Ciclosporin-dependent, nu-independent, mucosal interleukin 6 response to gram-negative bacteria

Regulation of the mucosal inflammatory response to Gram-negative bacteria was analysed. The interleukin 6 (IL-6) secretion, influx of polymorphonuclear leucocytes into urine, and bacterial clearance from the kidneys were compared between Balb/c (nu/nu) and nu/+/- mice, with and without ciclosporin (CsA) treatment. There was no significant influence of the nu genotype on any of the host responses measured. CsA pretreatment significantly decreased Il-6 secretion in both nu/nu and nu/+/- mice, but did not affect bacterial clearance or the leucocyte response in any mouse strain tested. Tissue damage, in addition to bacterial infection, resulted in significantly higher levels of IL-6 than bacterial infection alone. Tissue-damaged mice were significantly less likely to clear the bacterial infection than their non-damaged counterparts, but there was no significant difference in the leucocyte response. CsA pretreatment did not significantly reduce the levels of IL-6 in the tissue-damaged mice. These results demonstrate that the mucosal inflammatory response to Gram-negative infection, including IL-6 secretion, is nu-independent, and that bacterial infection alone or in combination with tissue damage induce IL-6 secretion by two different pathways.