Cytokine mRNA expression and serum cortisol evaluation during murine lung inflammation induced by Mycobacterium tuberculosis

A model system was characterized for investigating the potential role of co rtisol in MTB induced immunopathology. Serum cortisol levels were evaluated in two mouse strains; C57BL/6 mice develop lung granulomas following acute Mycobacterium tuberculosis infection while A/J mice are deficient in this process. Serum cortisol levels were examined post infection, as well as imm unoregulatory mRNA expression in the lung, measured using bioluminescent RT -PCR techniques. Prior to infection, the A/J mice constitutively maintain n early 75% higher serum cortisol than C57BL/6 mice. Both A/J and C57BL/6 mic e exhibited approximately 30% reduction in relative serum cortisol followin g infection. At no time did serum cortisol levels in the A/J fall below con stitutive levels in the non-infected C57BL/6. The overall elevated cortisol in the A/J may affect pulmonary immunoresponsiveness; A/J mice exhibited e arlier induction of IL-10 and TNF-alpha than C57BL/6 mice, with a relative lack of IL-2 during late infection. Conversely, the C57BL/6 mice demonstrat ed higher IL-12(p40) and IL-2 messages at the latter stages of disease than the A/J mice. Both mice demonstrated high IFN-gamma mRNA. The high constit utive serum cortisol in the A/J mice may therefore contribute to establishm ent of an environment counter-productive to initiation of protective Th1 ce ll and granulomatous responses.