• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Oncol Nurs Forum. Author manuscript; available in PMC Jun 13, 2011.
Published in final edited form as:
PMCID: PMC3113554
NIHMSID: NIHMS297034

Does Muscle-Derived Interleukin-6 Mediate Some of the Beneficial Effects of Exercise on Cancer Treatment–Related Fatigue?

Lisa J. Wood, PhD, RN, Lillian M. Nail, PhD, RN, FAAN, and Kerri A. Winters, PhD

Abstract

Purpose/Objectives

To review evidence that muscle-derived interleukin-6 (IL-6) mediates some of the beneficial effects of exercise on cancer treatment–related fatigue (CTRF).

Data Sources

Electronic nursing, psychology, and medicine databases.

Data Synthesis

Fatigue is a common and often debilitating symptom associated with cancer treatment. Although the molecular mechanisms underlying CTRF have yet to be fully elucidated, it may be akin to the fatigue associated with “sickness behavior,” which is initiated by the production of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). Physical exercise has been shown to decrease fatigue levels in patients with cancer undergoing treatment. Skeletal muscle selectively produces IL-6 during exercise, and muscle-derived IL-6 can decrease the production and activity of IL-1β and TNF-α. Thus, the anti-inflammatory effects of muscle-derived IL-6 may be a mechanism underlying the observed beneficial effects of exercise on CTRF.

Conclusions

Further studies are needed to determine whether the anti-inflammatory effects of exercise underlie its beneficial effects on CTRF.

Implications for Nursing

Nurses have proven to be leaders in the field of cancer symptom management. An understanding of potential mechanisms underlying the beneficial effects of exercise on CTRF may help to fine-tune exercise interventions to maximize symptom control and to identify new treatment strategies for fatigued patients with cancer who are unable to participate in an exercise program.

Fatigue is a common and often debilitating symptom associated with cancer treatment. Although the molecular mechanisms underlying cancer treatment–related fatigue (CTRF) have yet to be fully elucidated, it may be homologous to the fatigue associated with “sickness behavior,” a cluster of symptoms caused by the production of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). Physical exercise has been shown to decrease fatigue levels in patients with cancer undergoing treatment. Yet the mechanisms underlying this benefit are unclear. This article discusses recent observations regarding the secretion of interleukin-6 (IL-6) by exercising muscle, its anti-inflammatory effects, and its potential relevance to the beneficial effects of exercise on CTRF.

Overview of Concepts

“Cancer-related fatigue is a distressing persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning” (National Comprehensive Cancer Network, 2009, p. FT-1). Fatigue often begins at the start of treatment and is the most common symptom experienced by patients undergoing cancer treatment (Irvine, Vincent, Graydon, Bubela, & Thompson, 1994). Given the effect that CTRF has on physical functioning and quality of life, its management is a crucial component of the cancer treatment plan. Although the cause of CTRF remains unclear, it may be the same as sickness behavior, a normal physiologic response to infection or tissue injury that is initiated by the production of IL-1β and TNF-α by immune cells (Dantzer & Kelley, 2007; Wood, Nail, Gilster, Winters, & Elsea, 2006). In a healthy individual, serum levels of IL-1β and TNF-α are low or undetectable (0–10 pg/ml). However, in response to immune challenge (e.g., infection, tissue damage), serum levels of IL-1β and TNF-α increase 10- to 100-fold, depending on the magnitude of the immune stimulus. IL-1β and TNF-α, in turn, trigger the production of IL-6, leading to an increase in serum levels of the cytokines (Mant et al., 2008). Although a direct role for the cytokines in CTRF has yet to be demonstrated, indirect evidence supports the idea. First, patients with cancer undergoing treatment often experience several symptoms, including anorexia, cachexia, pain, sleep disturbance, and depression, which can affect the subjective sensation of fatigue. Considerable evidence has been generated in animal models and in clinical populations that IL-1β, TNF-α, and IL-6 play a significant role in the etiology of those symptoms (Wood, Nail, Gilster, et al., 2006). Second, cytotoxic chemotherapeutic agents and whole-body or localized radiation can induce the production of inflammatory cytokines in isolated immune cells and when administered to experimental animals (Ding, Porteu, Sanchez, & Nathan, 1990; Muhl et al., 1999; White, Martin, Lee, Haskill, & Ting, 1998; Wood, Nail, Perrin, et al., 2006). The stimulus for inflammatory cytokine production may be related, in part, to cancer treatment–mediated activation of p38 mitogen–activated protein kinase (p38 MAPK), a cellular enzyme that plays a central role in the production of inflammatory cytokines and the development of sickness behavior (Badger et al., 1996; Branger et al., 2002; Elsea, Roberts, Druker, & Wood, 2008). Third, increased blood levels of several inflammatory markers, including IL-6, have been demonstrated in fatigued patients with cancer (Schubert, Hong, Natarajan, Mills, & Dimsdale, 2007). Fourth, fatigue is common in chronic inflammatory diseases. For instance, the fatigue associated with Castleman disease (a rare lymphoproliferative disorder in which increased secretion of IL-6 by lymphoid cells is believed to play an important role) can be decreased by administration of monoclonal antibodies that block the activity of IL-6 (Nishimoto et al., 2005). Fatigue also is a common symptom of rheumatoid arthritis (RA). Proinflammatory cytokines such as TNF-α have been implicated in the etiology of RA (Goldblatt & Isenberg, 2005), and monoclonal antibodies that block the activity of the cytokine in the blood and synovial fluid of the affected joint have proven effective in reducing the severity of disease and levels of fatigue (Omdal & Gunnarsson, 2004; Weinblatt et al., 2003). In addition to RA, diabetes and cardiovascular disease are associated with low-grade systemic inflammation. Indeed, chronic production of TNF-α, IL-1β, and IL-6 have been implicated in the etiology of those disorders (Andersen & Pedersen, 2008).

The Role of Physical Exercise

Regular moderate exercise reduces systemic inflammation and, consequently, improves health outcomes in RA, cardiovascular disease, and diabetes (Lundberg & Nader, 2008; Pedersen, 2006). For more than a decade, physical exercise has been known to have similar beneficial effects with regard to fatigue in patients with cancer undergoing treatment (Mock et al., 1997). Although several studies since have supported those earlier findings, others have not (Cramp & Daniel, 2008). Exercise may decrease fatigue by stimulating neuromuscular function and producing hemodynamic changes (Schwartz, 1998), reducing depression and anxiety (Segar et al., 1998), or reducing social isolation (Bower, Ganz, Aziz, & Fahey, 2002; Michael, Kawachi, Berkman, Holmes, & Colditz, 2000). Another explanation for the beneficial effect of exercise on CTRF is that exercise stimulates an anti-inflammatory cascade that decreases the biologic activity of fatigue-causing IL-1β and TNF-α. The relationship among CTRF, IL-1β, TNF-α, and exercise is illustrated in Figure 1. Understanding whether muscle-derived IL-6 mediates the beneficial effects of physical exercise on CTRF by decreasing levels of IL-1β and TNF-α would allow researchers and clinicians to fine-tune future exercise interventions to achieve maximum symptom control. Furthermore, physical exercise may be an unachievable goal for some patients with cancer undergoing treatment. For such individuals, understanding whether exercise reduces fatigue by decreasing the production of fatigue-causing IL-1β and TNF-α could lead to therapeutic strategies using drugs to target the cytokines, thereby decreasing fatigue.

Figure 1
Proposed Mechanism Underlying the Beneficial Effects of Exercise on Cancer Treatment–Related Fatigue

Skeletal Muscle and Interleukin-6

Skeletal muscle is the largest organ in the body that produces IL-6 in response to exercise (Steensberg et al., 2000). Serum levels of IL-6 rise rapidly during exercise, followed by a complete decline to baseline levels soon thereafter. The pattern of expression of IL-6 during non–muscle-damaging exercise is shown in Figure 2A. When the IL-6 response to exercise first emerged, researchers believed that its production was related to exercise-induced muscle damage (Bruunsgaard et al., 1997). In contrast to low-intensity exercise that does not lead to muscle fiber damage, the response to high-intensity or unaccustomed muscle-damaging exercise is typically accompanied by a systemic cytokine response that is similar to infection and includes elevated serum levels of IL-1β and TNF-α and, in turn, IL-6 (Ostrowski, Rohde, Asp, Schjerling, & Pedersen, 1999). The source of these serum cytokines in the context of muscle damage is likely macrophages and neutrophils that rapidly infiltrate the damaged muscle (Tidball, 2005). In addition, muscle cells have the innate ability to produce IL-1β, TNF-α and IL-6 themselves in response to harmful stimuli such as infection (Lang, Silvis, Deshpande, Nystrom, & Frost, 2003). The pattern of expression of IL-1β, TNF-α, and, consequently, IL-6 following muscle-damaging exercise is shown in Figure 2B. Of note is the fact that in contrast to non–muscle-damaging exercise, when IL-6 levels rapidly peak and then fall to baseline levels soon after the end of exercise (see Figure 2A), a second surge of IL-6 is evident following muscle-damaging exercise, usually of decreased magnitude (see Figure 2B). In that case, its production is triggered by IL-1β and TNF-α (see Figure 2B). In addition, creatine kinase, a widely used indirect marker of muscle fiber damage, also is elevated two to three days following muscle-damaging exercise (Clarkson, Kearns, Rouzier, Rubin, & Thompson, 2006).

Figure 2
Approximation of the Kinetics of Interleukin-1 Beta (IL-1β), Tumor Necrosis Factor Alpha (TNF-α), and Interleukin-6 (IL-6) in Serum During Two Types of Exercise

Subsequent studies challenged the notion that IL-6 response to exercise was related to muscle damage because the same IL-6 response was evident in its absence (Ostrowski, Hermann, et al., 1998; Ostrowski, Rohde, Zacho, Asp, & Pedersen, 1998; Steensberg et al., 2002). That finding led to the idea that the source of IL-6 produced during non–muscle-damaging exercise is muscle cells responding to contraction and energy depletion (Steensberg et al., 2000). Indeed, IL-6 is an important regulator of glucose and amino acid homeostasis and fat metabolism (for reviews, see Pedersen & Fischer, 2007). Consistent with this idea is the finding that magnitude of the IL-6 response is related to the intensity, duration, and type of exercise (Brenner et al., 1999; Ostrowski, Schjerling, & Pedersen, 2000) but not muscle mass (Toft et al., 2002). In addition, higher levels of IL-6 are released from exercising skeletal muscle in conditions of low- compared to high-glycogen conditions (Keller et al., 2001).

Muscle-Derived Interleukin-6 as a Mediator of the Anti-Inflammatory Effects of Exercise

Exercise-induced increases in IL-6 may mediate the anti-inflammatory effects of exercise. This idea may seem paradoxical because IL-6 often is considered proinflammatory in nature, playing an intimate role with IL-1β and TNF-α in the induction of sickness behavior. Moreover, increased blood levels of IL-6 have been reported in fatigued cancer survivors (Schubert et al., 2007) and in those with atherosclerosis and diabetes (Tilg & Moschen, 2006). Yet substantial evidence shows that IL-6 has anti-inflammatory properties in that it decreases the production or activity of IL-1β and TNF-α. For instance, infusion of IL-6 prior to endotoxin administration in healthy people has been shown to decrease plasma levels of TNF-α (Febbraio et al., 2003). Moreover, exercise-induced IL-6 production can decrease TNF-α levels in muscle of TNF-α transgenic mice (Keller, Keller, Giralt, Hidalgo, & Pedersen, 2004). Thus, the observed increase in blood IL-6 levels in CTRF and cardiovascular disease may reflect persistent IL-1β and TNF-α production on a local level that, in turn, triggers the systemic production of IL-6. IL-6 mediates its own anti-inflammatory effects by stimulating both the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, the end result of which is the increased production of several molecules with anti-inflammatory properties, namely growth hormone, cortisol, interleukin-10 (IL-10), and interleukin-1 receptor agonist (IL-1RA) (see Figure 3).

Figure 3
Anti-Inflammatory Cascade

Hypothalamic-Pituitary-Adrenal Axis

Activation of the HPA axis occurs following a stressor, such as high-intensity exercise. Cortisol is a marker of HPA axis activation. At the start of exercise, serum cortisol rises rapidly and peaks just after exercise has stopped (Paiva, Deodhar, Jones, & Bennett, 2002). Within an hour of exercise, serum cortisol levels return to baseline. Thus, the pattern of cortisol secretion during exercise parallels that of IL-6. This observation led to the idea that circulating IL-6 stimulates cortisol release or vice versa. Studies in which IL-6 was infused into healthy, resting adults demonstrated that the former is likely the case. IL-6 infusion triggers the production and release of cortisol from the adrenal cortex, leading to its accumulation in the circulation (Steensberg, Fischer, Keller, Moller, & Pedersen, 2003). Cortisol is believed to exert its anti-inflammatory effects by increasing the production of the anti-inflammatory cytokines IL-1RA and IL-10 (Barber et al., 1995; Dandona, Aljada, Garg, & Mohanty, 1999).

The Immune System

IL-6 infusion in healthy individuals increases serum levels of IL-1RA, which competes with IL-1β for binding to the IL-1β receptor, therefore blocking the activity of IL-1β (Steensberg et al., 2003). Although the source of IL-1RA following IL-6 infusion is unclear, primary sources of this cytokine during infection are monocytes and macrophages. IL-6 also induces the production of IL-10 (Steensberg et al., 2003). IL-10 is another cytokine with potent anti-inflammatory properties (de Waal Malefyt, Abrams, Bennett, Figdor, & de Vries, 1991). It is produced by several types of immune cells, including specific T helper cell lymphocytes, monocytes, and B cells. IL-10 blocks the synthesis of several cytokines, including IL-1β, TNF-α, and IL-6 (Thomassen, Divis, & Fisher, 1996), and its ability to reduce the synthesis of these cytokines likely explains its ability to protect mice from a lethal dose of endotoxin in a mouse model of septic shock (Gerard et al., 1993). Not surprisingly, IL-10–deficient mice display an exaggerated TNF-α response to infection (Holscher et al., 2000). Taken together, substantial evidence suggests an anti-inflammatory role for IL-6 that balances the activity of IL-1β and TNF-α to attain homeostasis.

Conclusions and Future Research

Compelling evidence exists that proinflammatory cytokines such as IL-1β and TNF-α play a role in the development of CTRF. Exercise is beneficial in the management of CTRF, yet why is unclear. The ability of exercise to decrease the production or activity of fatigue-causing cytokines may be one mechanism underlying the observed beneficial effects of exercise on CTRF. Although strong evidence exists that different cancer treatments can increase the production of inflammatory cytokines, few clinical studies have demonstrated a clear relationship between inflammatory cytokines and CTRF. Emerging longitudinal studies aimed at examining the relationship between changes in blood levels of inflammatory cytokines and changes in fatigue levels may help to support a role for an immunologic basis to CTRF. Such studies also could provide a platform on which to determine whether the anti-inflammatory effects of exercise underlie its beneficial effects on CTRF. Findings from such studies may help further refine exercise interventions for maximal symptom control in patients with cancer and may aid in the identification of biologic factors that mediate the beneficial effects of exercise on CTRF. Importantly, identifying the molecular determinants could lead to new treatment strategies for fatigued patients with cancer who are unable to participate in an exercise program.

Footnotes

This material is protected by U.S. copyright law. Unauthorized reproduction is prohibited. To purchase quantity reprints, please e-mail gro.sno@stnirper or to request permission to reproduce multiple copies, please e-mail gro.sno@snoissimrepbup.

No financial relationships to disclose.

Copyright of Oncology Nursing Forum is the property of Oncology Nursing Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder’s express written permission. However, users may print, download, or email articles for individual use.

References

  • Andersen K, Pedersen BK. The role of inflammation in vascular insulin resistance with focus on Il-6. Hormone and Metabolic Research. 2008;40(9):635–639. [PubMed]
  • Badger AM, Bradbeer JN, Votta B, Lee JC, Adams JL, Griswold DE. Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock, and immune function. Journal of Pharmacology and Experimental Therapeutics. 1996;279(3):1453–1461. [PubMed]
  • Barber AE, Coyle SM, Fischer E, Smith C, van der Poll T, Shires GT, et al. Influence of hypercortisolemia on soluble tumor necrosis factor receptor II and interleukin-1 receptor antagonist responses to endotoxin in human beings. Surgery. 1995;118(2):406–410. [PubMed]
  • Bower JE, Ganz PA, Aziz N, Fahey JL. Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosomatic Medicine. 2002;64(4):604–611. [PubMed]
  • Branger J, van den Blink B, Weijer S, Madwed J, Bos CL, Gupta A, et al. Anti-inflammatory effects of a p38 mitogen-activated protein kinase inhibitor during human endotoxemia. Journal of Immunology. 2002;168(8):4070–4077. [PubMed]
  • Brenner IK, Natale VM, Vasiliou P, Moldoveanu AI, Shek PN, Shephard RJ. Impact of three different types of exercise on components of the inflammatory response. European Journal of Applied Physiology and Occupational Physiology. 1999;80(5):452–460. [PubMed]
  • Bruunsgaard H, Galbo H, Halkjaer-Kristensen J, Johansen TL, MacLean DA, Pedersen BK. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. Journal of Physiology. 1997;499(Pt. 3):833–841. [PMC free article] [PubMed]
  • Clarkson PM, Kearns AK, Rouzier P, Rubin R, Thompson PD. Serum creatine kinase levels and renal function measures in exertional muscle damage. Medicine and Science in Sports and Exercise. 2006;38(4):623–627. [PubMed]
  • Cramp F, Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database of Systematic Reviews. 2008;2 CD006145. [PubMed]
  • Dandona P, Aljada A, Garg R, Mohanty P. Increase in plasma interleukin-10 following hydrocortisone injection. Journal of Clinical Endocrinology and Metabolism. 1999;84(3):1141–1144. [PubMed]
  • Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain, Behavior, and Immunity. 2007;21(2):153–160. [PMC free article] [PubMed]
  • de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes. Journal of Experimental Medicine. 1991;174(5):1209–1220. [PMC free article] [PubMed]
  • Ding AH, Porteu F, Sanchez E, Nathan CF. Shared actions of endotoxin and taxol on TNF receptors and TNF release. Science. 1990;248(4953):370–372. [PubMed]
  • Elsea CR, Roberts DA, Druker BJ, Wood LJ. Inhibition of p38 MAPK suppresses inflammatory cytokine induction by etoposide, 5-fluorouracil, and doxorubicin without affecting tumoricidal activity. PLoS ONE. 2008;3(6):e2355. [PMC free article] [PubMed]
  • Febbraio MA, Steensberg A, Keller C, Starkie RL, Nielsen HB, Krustrup P, et al. Glucose ingestion attenuates interleukin-6 release from contracting skeletal muscle in humans. Journal of Physiology. 2003;549(Pt. 2):607–612. [PMC free article] [PubMed]
  • Gerard C, Bruyns C, Marchant A, Abramowicz D, Vandenabeele P, Delvaux A, et al. Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. Journal of Experimental Medicine. 1993;177(2):547–550. [PMC free article] [PubMed]
  • Goldblatt F, Isenberg DA. New therapies for rheumatoid arthritis. Clinical and Experimental Immunology. 2005;140(2):195–204. [PMC free article] [PubMed]
  • Holscher C, Mohrs M, Dai WJ, Kohler G, Ryffel B, Schaub GA, et al. Tumor necrosis factor alpha-mediated toxic shock in Trypanosoma cruzi-infected interleukin 10-deficient mice. Infection and Immunity. 2000;68(7):4075–4083. [PMC free article] [PubMed]
  • Irvine D, Vincent L, Graydon JE, Bubela N, Thompson L. The prevalence and correlates of fatigue in patients receiving treatment with chemotherapy and radiotherapy. A comparison with the fatigue experienced by healthy individuals. Cancer Nursing. 1994;17(5):367–378. [PubMed]
  • Keller C, Keller P, Giralt M, Hidalgo J, Pedersen BK. Exercise normalizes overexpression of TNF-alpha in knockout mice. Biochemical and Biophysical Research Communications. 2004;321(1):179–182. [PubMed]
  • Keller C, Steensberg A, Pilegaard H, Osada T, Saltin B, Pedersen BK, et al. Transcriptional activation of the Il-6 gene in human contracting skeletal muscle: Influence of muscle glycogen content. Faseb Journal. 2001;15(14):2748–2750. [PubMed]
  • Lang CH, Silvis C, Deshpande N, Nystrom G, Frost RA. Endotoxin stimulates in vivo expression of inflammatory cytokines tumor necrosis factor alpha, interleukin-1beta, -6, and high-mobility-group protein-1 in skeletal muscle. Shock. 2003;19(6):538–546. [PubMed]
  • Lundberg IE, Nader GA. Molecular effects of exercise in patients with inflammatory rheumatic disease. Nature Clinical Practice. Rheumatology. 2008;4(11):597–604. [PubMed]
  • Mant TG, Borozdenkova S, Bradford DB, Allen E, Amin DM, Toothaker RD, et al. Changes in HLA-DR expression, cytokine production, and coagulation following endotoxin infusion in healthy human volunteers. International Immunopharmacology. 2008;8(5):701–707. [PubMed]
  • Michael YL, Kawachi I, Berkman LF, Holmes MD, Colditz GA. The persistent impact of breast carcinoma on functional health status: Prospective evidence from the Nurses’ Health Study. Cancer. 2000;89(11):2176–2186. [PubMed]
  • Mock V, Dow KH, Meares CJ, Grimm PM, Dienemann JA, Haisfield-Wolfe ME, et al. Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer. Oncology Nursing Forum. 1997;24(6):991–1000. [PubMed]
  • Muhl H, Nold M, Chang JH, Frank S, Eberhardt W, Pfeilschifter J. Expression and release of chemokines associated with apoptotic cell death in human promonocytic U937 cells and peripheral blood mononuclear cells. European Journal of Immunology. 1999;29(10):3225–3235. [PubMed]
  • National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology™: Cancer-related fatigue. Jenkintown, PA: Author; 2009. [v.1.2009].
  • Nishimoto N, Kanakura Y, Aozasa K, Johkoh T, Nakamura M, Nakano S, et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood. 2005;106(8):2627–2632. [PubMed]
  • Omdal R, Gunnarsson R. The effect of interleukin-1 blockade on fatigue in rheumatoid arthritis—A pilot study. Rheumatology International. 2004;25(6):481–484. [PubMed]
  • Ostrowski K, Hermann C, Bangash A, Schjerling P, Nielsen JN, Pedersen BK. A trauma-like elevation of plasma cytokines in humans in response to treadmill running. Journal of Physiology. 1998;513(Pt. 3):889–894. [PMC free article] [PubMed]
  • Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. Journal of Physiology. 1999;515(Pt. 1):287–291. [PMC free article] [PubMed]
  • Ostrowski K, Rohde T, Zacho M, Asp S, Pedersen BK. Evidence that interleukin-6 is produced in human skeletal muscle during prolonged running. Journal of Physiology. 1998;508(Pt. 3):949–953. [PMC free article] [PubMed]
  • Ostrowski K, Schjerling P, Pedersen BK. Physical activity and plasma interleukin-6 in humans—Effect of intensity of exercise. European Journal of Applied Physiology. 2000;83(6):512–515. [PubMed]
  • Paiva ES, Deodhar A, Jones KD, Bennett R. Impaired growth hormone secretion in fibromyalgia patients: Evidence for augmented hypothalamic somatostatin tone. Arthritis and Rheumatism. 2002;46(5):1344–1350. [PubMed]
  • Pedersen BK. The anti-inflammatory effect of exercise: Its role in diabetes and cardiovascular disease control. Essays in Biochemistry. 2006;42:105–117. [PubMed]
  • Pedersen BK, Fischer CP. Physiological roles of muscle-derived interleukin-6 in response to exercise. Current Opinion in Clinical Nutrition and Metabolic Care. 2007;10(3):265–271. [PubMed]
  • Schubert C, Hong S, Natarajan L, Mills PJ, Dimsdale JE. The association between fatigue and inflammatory marker levels in cancer patients: A quantitative review. Brain, Behavior, and Immunity. 2007;21(4):413–427. [PubMed]
  • Schwartz AL. Patterns of exercise and fatigue in physically active cancer survivors. Oncology Nursing Forum. 1998;25(3):485–491. [PubMed]
  • Segar ML, Katch VL, Roth RS, Garcia AW, Portner TI, Glickman SG, et al. The effect of aerobic exercise on self-esteem and depressive and anxiety symptoms among breast cancer survivors. Oncology Nursing Forum. 1998;25(1):107–113. [PubMed]
  • Steensberg A, Fischer CP, Keller C, Moller K, Pedersen BK. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. American Journal of Physiology Endocrinology and Metabolism. 2003;285(2):E433–E437. [PubMed]
  • Steensberg A, Keller C, Starkie RL, Osada T, Febbraio MA, Pedersen BK. IL-6 and TNF-alpha expression in, and release from, contracting human skeletal muscle. American Journal of Physiology Endocrinology and Metabolism. 2002;283(6):E1272–E1278. [PubMed]
  • Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Klarlund Pedersen B. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. Journal of Physiology. 2000;529(Pt. 1):237–242. [PMC free article] [PubMed]
  • Thomassen MJ, Divis LT, Fisher CJ. Regulation of human alveolar macrophage inflammatory cytokine production by interleukin-10. Clinical Immunology and Immunopathology. 1996;80(3, Pt. 1):321–324. [PubMed]
  • Tidball JG. Inflammatory processes in muscle injury and repair. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2005;288(2):R345–R353. [PubMed]
  • Tilg H, Moschen AR. Adipocytokines: Mediators linking adipose tissue, inflammation, and immunity. Nature Reviews. Immunology. 2006;6(10):772–783. [PubMed]
  • Toft AD, Jensen LB, Bruunsgaard H, Ibfelt T, Halkjaer-Kristensen J, Febbraio M, et al. Cytokine response to eccentric exercise in young and elderly humans. American Journal of Physiology Cell Physiology. 2002;283(1):C289–C295. [PubMed]
  • Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: The ARMADA trial. Arthritis and Rheumatism. 2003;48(1):35–45. [PubMed]
  • White CM, Martin BK, Lee LF, Haskill JS, Ting JP. Effects of paclitaxel on cytokine synthesis by unprimed human monocytes, T lymphocytes, and breast cancer cells. Cancer Immunology and Immunotherapy. 1998;46(2):104–112. [PubMed]
  • Wood LJ, Nail LM, Gilster A, Winters KA, Elsea CR. Cancer chemotherapy-related symptoms: Evidence to suggest a role for proinflammatory cytokines. Oncology Nursing Forum. 2006;33(3):535–542. [PubMed]
  • Wood LJ, Nail LM, Perrin NA, Elsea CR, Fischer A, Druker BJ. The cancer chemotherapy drug etoposide (VP-16) induces proinflammatory cytokine production and sickness behavior-like symptoms in a mouse model of cancer chemotherapy-related symptoms. Biological Research for Nursing. 2006;8(2):157–169. [PubMed]
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...