Different expression of cytokines and receptors in bleomycin-sensitive and resistant mice

The sensitivity to the fibrosis-inducing effect of bleomycin (BLM) varies considerably from species to species, and the variability of the response in different strains of mice is well documented. The reasons for such varied responses are not known. Recent evidence indicates that the up-regulated expression of cytokines and receptors may be involved. We evaluated the expression pattern of some cytokines and of their receptors in C57Bl/6J BLM-sensitive and Balb/C BLM-resistant mice. Animals from both strains received either saline (50µl), or BLM (0.1U/50µl) intratracheally. The mice were sacrificed at various times after the treatment. The lungs were analysed for cytokine and cytokine receptors mRNA by Ribonuclease Protected Assay. A significant increased expression (over saline-treated-animals) of TNF-alpha and IL-1 beta mRNA was observed in both strains at 8 hours. However, BLM resulted in an up-regulated lung expression for TNF-alpha and IL-1 receptors, only in C57Bl/6J sensitive animals. This profile is evident from 63 hours onward. In addition to TNF-alpha, BLM also resulted in the up-regulated expression of TGF-beta in the lungs of both strains at 8 hours, and in an enhanced expression of TGF-beta receptors I and II in only C57Bl/6J mice. The up-regulation of the TGF-beta receptor expression was preceded in this strain by an increased expression of IL-4, IL-13 and IL-13 receptor alpha1 at 8 hours after BLM. The difference we observed in the cytokine profile may offer an addidional explanation for the different fibrogenic response of the two mouse strains to BLM.