A model system was characterized for investigating the potential role of
cortisol 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 immunoregulatory
mRNA expression in the lung, measured using bioluminescent RT-PCR techniques. Prior to
infection, the A/J mice constitutively maintain nearly 75&percent; higher serum
cortisol than C57BL/6 mice. Both A/J and C57BL/6 mice exhibited approximately 30&percent; reduction in relative serum
cortisol following
infection. At no time did serum
cortisol levels in the A/J fall below constitutive levels in the non-infected C57BL/6. The overall elevated
cortisol in the A/J may affect pulmonary immunoresponsiveness; A/J mice exhibited earlier 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 demonstrated higher IL-12(p40) and
IL-2 messages at the latter stages of disease than the A/J mice. Both mice demonstrated high IFN-&gama;
mRNA. The high constitutive serum
cortisol in the A/J mice may therefore contribute to establishment of an environment counter-productive to initiation of protective Th1 cell and granulomatous responses.