Role of interleukin-4 and prostaglandin E2 in Leishmania amazonensis infection of BALB/c mice.
The role of cytokines in Leishmania amazonensis experimental infection has not been as well studied as in Leishmania major infection model. Here we investigated the role of interleukin (IL)-4 and PGE(2) in L. amazonensis infection of susceptible BALB/c mice. IL-4 deficient (-/-) or wild-type (+/+) BALB/c mice were infected with different inocula of L. amazonensis. Two weeks after infection with 5x10(6) promastigotes/footpad, the production of interferon (IFN)-gamma upon L. amazonensis antigen stimulation was significantly higher in lymph node cell cultures of IL-4-/- mice than in IL-4+/+ mice. The levels of anti-leishmania IgG2a antibodies were also significantly higher in serum from IL-4-/- mice. In contrast, the levels of IgG1 antibodies were increased in IL-4+/+ mice and almost undetectable in IL-4-/- mice. Despite the increased Th1 response, lesions of IL-4-/- BALB/c mice progressed similarly to those of IL-4+/+ mice upon infection with the 5x10(6) inoculum. However, IL-4-/- mice developed smaller lesions upon infection with 10(5), 10(4) or 10(3) parasites than IL-4+/+ mice. The resistance of IL-4-/- correlated with higher Th1 response, compared to IL-4+/+ upon infection with 10(4)L. amazonensis. IL-4+/+ mice treated with indomethacin, an inhibitor of PGE(2) synthesis, during the first 3weeks of infection developed smaller lesions and lower parasitic load when compared to the control group. The lesions of indomethacin-treated groups contained mostly macrophages without vacuoles and small or absent necrotic areas. These results indicate that IL-4 and PGE(2) are susceptibility factors to L. amazonensis infection.
Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Rua Waldemar Falcão 121, 40296-710 Salvador, Bahia, Brazil.
Elisalva T
ET
Guimarães
Luana A
LA
Santos
Ricardo
R
Ribeiro dos Santos
Mauro M
MM
Teixeira
Washington L C
WL
dos Santos
Milena B P
MB
Soares
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism*; D007894:Leishmania mexicana / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015847:Interleukin-4; D007371:Interferon-gamma; D015232:Dinoprostone; D007213:Indomethacin