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 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.
Actor
J K
JK
Department of Pathology, University of Texas-Houston Medical School, Texas 77030, USA. Jeffrey.K.Actor@uth.tmc.edu
Leonard
C D
CD
Watson
V E
VE
Wells
A
A
Jagannath
C
C
Hunter
R L
RL
Dasgupta
A
A
D000818:Animals; D016207:Cytokines / Q000235:genetics*; D006854:Hydrocortisone / Q000097:blood*; D007375:Interleukin-1 / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008163:Luminescent Measurements; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009169:Mycobacterium tuberculosis; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000235:genetics* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D006854:Hydrocortisone