Home >> Combinatorial Chemistry & High Throughput Screening, Volume 3, Number 4

Cytokine mRNA Expression and Serum Cortisol Evaluation During Murine Lung Inflammation Induced by Mycobacterium tuberculosis

Authors: Actor J.K.; Leonard C.D.; Watson V.E.; Wells A.; Jagannath C.; Hunter Jr. R.L.; Dasgupta A.

Source: Combinatorial Chemistry & High Throughput Screening, Volume 3, Number 4, August 2000 , pp. 343-351(9)

Publisher: Bentham Science Publishers

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Abstract:

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% higher serum cortisol than C57BL/6 mice. Both A/J and C57BL/6 mice exhibited approximately 30% 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-a 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-g 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.

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  • Combinatorial Chemistry & High Throughput Screening publishes full length original research articles and reviews describing various topics in combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) and/or high throughput screening (e.g. developmental, practical or theoretical). Ancillary subjects of key importance, such as robotics and informatics, will also be covered by the journal. In these respective subject areas, Combinatorial Chemistry & High Throughput Screening is intended to function as the most comprehensive and up-to-date medium available. The journal should be of value to individuals engaged in the process of drug discoveryand development, in the settings of industry, academia or government.
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