Suppression of inflammation by cyclosporin A is mediated via a T lymphocyte-independent process.

An athymic mutant rat strain was used to examine the hypothesis that modification of diseases with an inflammatory component by cyclosporin A (CsA) results from the suppression of nonspecific inflammatory mechanisms, rather than T-lymphocyte function, as is commonly inferred. Confirmation that the animal host was grossly depleted of T cells was obtained from anatomic and morphologic examination and functional tests of T-lymphocyte responsiveness. The experimental approach was to determine the effect of CsA on the course of experimentally induced infection with Escherichia coli, and extracellular pathogen. Host protection against this microorganism is dependent on an effective nonspecific inflammatory response. CsA administration prior to bacterial challenge resulted in a highly significant increase in bacterial numbers in the kidneys of both euthymic and athymic hosts. The data have provided a direct demonstration that modulation of the nonspecific inflammatory response by CsA can occur via a T lymphocyte-independent process.