In vivo cytokine profiles in patients with kala-azar. Marked elevation of both interleukin-10 and interferon-gamma.
The immunological mechanisms underlying the susceptibility to disseminated visceral parasitism of mononuclear phagocytes in patients with kala-azar remain undefined. Resistance and susceptibility are correlated with distinct patterns of cytokine production in murine models of disseminated leishmanial disease. To assess lesional cytokine profiles in patients with kala-azar, bone marrow aspirates were analyzed using a quantitative reverse transcriptase PCR technique to amplify specific mRNA sequences of multiple Th1-, Th2-, and/or macrophage-associated cytokines. Transcript levels of IL-10 as well as IFN-gamma were significantly elevated in patients with active visceral leishmaniasis; IL-10 levels decreased markedly with resolution of disease. These findings suggest that IL-10, a potent, pleiotropic suppressor of all known microbicidal effector functions of macrophages, may contribute to the pathogenesis of kala-azar by inhibiting the cytokine-mediated activation of host macrophages that is necessary for the control of leishmanial infection.
Karp
C L
CL
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
el-Safi
S H
SH
Wynn
T A
TA
Satti
M M
MM
Kordofani
A M
AM
Hashim
F A
FA
Hag-Ali
M
M
Neva
F A
FA
Nutman
T B
TB
Sacks
D L
DL
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001853:Bone Marrow / Q000737:chemistry* / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D016753:Interleukin-10 / Q000032:analysis*; D007898:Leishmaniasis, Visceral / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000502:physiology
D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma