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Reg Immunol. 1993 May-Aug;5(3-4):207-17.

PCR analysis of cytokine induction profiles associated with mouse strain variation in susceptibility to pulmonary fibrosis.

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University of Rochester Cancer Center, NY 14642.


Susceptibility of mice to the induction of pulmonary fibrosis by bleomycin sulfate is inbred strain dependent, with C57BL/6 mice exhibiting high sensitivity to the drug and BALB/c mice demonstrating a resistant phenotype. The lungs of bleomycin treated C57BL/6J and BALB/cBy mice were analyzed for their mRNA expression level of a panel of cytokines using a semi-quantitative polymerase chain reaction (SQ-PCR) assay. Transforming growth factor-beta 1 (TGF-beta 1) mRNA was found to increase sevenfold by 5 days after bleomycin treatment of C57BL/6J (sensitive) mice. BALB/cBy (resistant) animals demonstrated a lower level of TGF-beta 1 mRNA induction, approximately threefold, after bleomycin administration. Analysis of interleukin-1 beta (IL-1 beta) mRNA levels also revealed a difference between the two strains, with BALB/cBy mice expressing approximately fourfold higher IL-1 beta mRNA levels than C57BL/6J mice. This result suggested possible protection by IL-1 beta. Analysis of (C57BL/6JxBALB/cBy)F1 hybrids, which are shown in this report to be sensitive to bleomycin-induced fibrosis, revealed a high IL-1 beta mRNA level, similar to that in the resistant parent. Thus, the observed strain variation in the level of IL-1 beta mRNA is not associated with differences in susceptibility to the induction of pulmonary fibrosis. In contrast, strain variation in interleukin-6 (IL-6) mRNA levels was observed that was completely concordant with the segregation of susceptibility phenotypes between the parental and F1 strains. This result indicates a possible association between sensitivity to bleomycin-induced fibrosis and inducibility of IL-6 mRNA upon drug treatment. Analysis of TGF-beta 2, interferon-gamma, interleukin-2, interleukin-3, and interleukin-4 (IL-4) mRNA showed no detectable strain variation in steady state mRNA levels in the lung as a consequence of bleomycin treatment. In contrast, the level of IL-4 receptor mRNA was induced to a higher degree in both sensitive groups (C57BL/6J and F1) than in resistant mice (BALB/cBy). Therefore, modulation of the IL-4 response, not at the level of IL-4 but through regulation of the IL-4 receptor, may play a role in pulmonary fibrogenesis.

[Indexed for MEDLINE]

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