Interleukin 10 production correlates with pathology in human Leishmania donovani infections.
We have found that an important Th2 cytokine, IL-10, is produced by tissues from patients acutely infected with Leishmania donovani. In all individuals tested, IL-10 mRNA production was increased in lymph nodes taken during acute disease over that observed in postacute samples. In contrast, both pre- and posttreatment lymph nodes had readily detected mRNA for IFN-gamma and IL-2. A down-regulating effect of IL-10 on leishmania-induced proliferative responses was demonstrated when Hu rIL-10 was added to cultures of PBMC from clinically cured individuals. PBMC from individuals with acute visceral leishmaniasis responded to stimulation with leishmania lysate by producing IL-10 mRNA. Simultaneously cultured PBMC collected from the same patients after successful chemotherapy produced no detectable IL-10 mRNA after leishmania antigen stimulation. Neutralizing anti-IL-10 mAb added to PBMC from patients with acute visceral leishmaniasis markedly increased the proliferative response to leishmania lysate. Finally, we observed mRNA for IL-10 and IFN-gamma concurrently in a lesion from a patient with post-kala-azar dermal leishmaniasis (PKDL). These results indicate the production of IL-10 during L. donovani infection, and suggest a role for this cytokine in the regulation of immune responsiveness during visceral leishmaniasis.
Ghalib
H W
HW
University of Juba, College of Medicine, Khartoum, Sudan.
Piuvezam
M R
MR
Skeiky
Y A
YA
Siddig
M
M
Hashim
F A
FA
el-Hassan
A M
AM
Russo
D M
DM
Reed
S G
SG
D000818:Animals; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000502:physiology; D007893:Leishmania donovani / Q000472:pathogenicity*; D007898:Leishmaniasis, Visceral / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics
D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10