Cytokine responses and progression to active tuberculosis in HIV-1-infected Ugandans: a prospective study.
Identifying correlates of immunity or susceptibility to disease promotes understanding of pathogenesis and development of diagnostic tools, treatments, and vaccines. There is evidence that type 1 cytokine responses are associated with protection against tuberculosis, and suppression of type 1, or switching to type 2 responses, with susceptibility, but this has not been studied prospectively. We studied a cohort of 631 HIV-1-infected Ugandan adults. At enrollment we performed whole blood cultures for type 1 (interferon [IFN]-gamma, interleukin [IL]-2) and type 2/immunosuppressive (IL-5, IL-10) responses to mycobacterial antigens (purified protein derivative [PPD] and culture filtrate proteins [CFP]). The incidence of tuberculosis was not associated with IFN-gamma responses, but was higher among participants with IL-2 responses (adjusted rate ratios [RR]: PPD 3.48; CFP 3.99; P < 0.001). For tuberculin skin test-positive participants, high incidence was also associated with an IL-10 response to PPD (adjusted RR 6.24, P = 0.03); for those with a BCG scar, high incidence was associated with positive IL-5 responses (adjusted RRs: PPD 3.64, P = 0.006; CFP 3.44, P = 0.04). The association with IL-2 production may reflect a response to tuberculous infection or to activating disease; the associations with IL-10 and IL-5 are in keeping with the expected role of immunosuppressive or type 2 cytokines.
Elliott
Alison M
AM
Uganda Virus Research Institute, P.O. Box 49, Entebbe, Uganda. alison.tom@infocom.co.ug
Hodsdon
Wendy S
WS
Kyosiimire
Jacqueline
J
Quigley
Maria A
MA
Nakiyingi
Jessica S
JS
Namujju
Proscovia B
PB
Watera
Christine
C
French
Neil
N
Gilks
Charles F
CF
Dockrell
Hazel M
HM
Whitworth
James A G
JA
D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D015994:Incidence; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology; D015848:Interleukin-5 / Q000097:blood / Q000276:immunology; D008297:Male; D011446:Prospective Studies; D014376:Tuberculosis / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000453:epidemiology / Q000276:immunology; D014454:Uganda / Q000453:epidemiology
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D016753:Interleukin-10; D007371:Interferon-gamma