In vivo porcine lipopolysaccharide inflammation models to study immunomodulation of drugs

Lipopolysaccharide (LPS), a structural part of the outer membrane of Gram-negative bacteria, is one of the most effective stimulators of the immune system and has been widely applied in pigs as an experimental model for bacterial infection. For this purpose, a variety of Escherichia coli serotypes, LPS doses, routes and duration of administration have been used. LPS administration induces the acute phase response (APR) and is associated with dramatic hemodynamic, clinical and behavioral changes in pigs. Pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin (IL)-1 and IL-6 are involved in the induction of the eicosanoid pathway and the hepatic production of acute phase proteins, including C-reactive protein (CRP), haptoglobin (Hp) and pig major acute phase protein (pig-MAP). Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) play a major role in the development of fever and pulmonary hypertension in LPS-challenged pigs, respectively. The LPS-induced APR can be modulated by drugs. Steroidal and nonsteroidal anti-inflammatory drugs ((N)SAIDs) possess anti-inflammatory, antipyretic and analgesic properties through (non)-selective central and peripheral cyclooxygenase (COX) inhibition. Antimicrobial drugs, especially macrolide antibiotics, which are commonly used in veterinary medicine for the treatment of bacterial respiratory diseases, have been recurrently reported to exert clinically important immunomodulatory effects in human and murine research. To investigate the influence of these drugs on the clinical response, production of pro-inflammatory cytokines, acute phase proteins (APP) and the course of the febrile response in pigs, in vivo LPS inflammation models can be applied. Yet, to date, in vivo research on the immunomodulatory properties of antimicrobial drugs in these models in pigs is largely lacking. This review provides acritical overview of the use of in vivo porcine E. coli LPS inflammation models for the study of the APR, as well as the potential immunomodulatory properties of anti-inflammatory and antimicrobial drugs in pigs.