NEUTROPHIL-MEDIATED INFLAMMATORY RESPONSE IN MURINE LUPUS

We have studied the ability of the lupus prone MRL lpr/lpr (MRL/lpr) a nd (NZBxNZW)F, (NZB/W) female mice to raise granulocyte mediated infla mmatory responses. These autoimmune strains, known to exhibit severe a nergy as concerns T cell dependent immune function, are not well analy sed with respect to neutrophil-mediated inflammatory responses. An in vivo model of granulocyte mediated inflammation has been developed in our laboratory. A single intradermal injection of olive oil into mouse footpad induces massive infiltration of polymorphonuclear cells (PMNC ) within 24 h. This extravasation of PMNC gives rise to a localized fo otpad swelling, which can be easily and reproducibly measured and rela tes to severity of the inflammatory process. T cell independence of th is inflammatory model was ascertained by in vivo T cell depletion usin g monoclonal antibodies to CD4 and CD8 molecules. Olive oil triggered inflammation was inducible in both young and aged lupus mice. The inte nsity of foot-pad swelling upon olive oil injection was similar in lup us mice and in healthy control strains. In contrast, aged MRL/lpr and NZB/W mice showed severely depressed T cell dependent inflammatory res ponses as assessed by delayed type hypersensitivity reaction to sheep red blood cells. We conclude that the PMNC mediated inflammatory poten tial is not affected in severely diseased lupus mice. The increased nu mbers of circulating PMNC together with intact PMNC function may expla in why severely immune deficient lupus mice seldom show clinical signs of bacterial infection.