Endogenous interleukin-18 is involved in immunity to Leishmania donovani but its absence does not adversely influence the therapeutic activity of sodium stibogluconate.
Immunity to Leishmania donovani is associated with an interleukin (IL)-12 driven T helper 1 (Th1) response. In addition, the ability to respond to chemotherapy with sodium stibogluconate (SSG) requires a fully competent immune response and both Th1 and Th2 responses have been shown to positively influence the outcome of drug treatment. In the present study, the influence of IL-18, which can modulate both interferon (IFN)-gamma and IL-4 production, on the outcome of primary L. donovani infection and SSG therapy following infection was assessed using BALB/c IL-18-deficient and wild type mice. IL-18 deficiency was associated with an increased susceptibility to L. donovani infection, evident by day 40 post infection, resulting in higher parasite burdens in the spleen, liver, and bone marrow compared with wild type control animals. Infected IL-18-deficient mice had significantly lower splenocyte concanavalin A (ConA) induced IFN-gamma production as well as lower serum IL-12 and IFN-gamma levels, indicating a reduced Th1 response. However, drug treatment was equally effective in both mouse strains and restored serum IL-12 and IFN-gamma levels, and IFN-gamma production by ConA stimulated splenocytes of IL-18-deficient mice, to levels equivalent to similarly treated wild type mice.
Mullen
Alexander B
AB
Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow, UK.
Lawrence
Catherine E
CE
McFarlane
Emma
E
Wei
Xiao-Quing
XQ
Carter
Katharine C
KC
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004198:Disease Susceptibility; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D020382:Interleukin-18 / Q000172:deficiency / Q000276:immunology*; D007893:Leishmania donovani / Q000276:immunology / Q000302:isolation & purification*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D016896:Treatment Outcome
D000913:Antibodies, Protozoan; D000981:Antiprotozoal Agents; D007074:Immunoglobulin G; D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma; D000967:Antimony Sodium Gluconate