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Ex vivo evidence for PGE2 and LTB4 involvement in cutaneous leishmaniasis: relation with infection status and cytokine production

Published online by Cambridge University Press:  06 April 2009

S. Milano ,
F. Arcoleo ,
M. Dieli ,
R. D'agostino ,
G. De Nucci ,
P. D'agostino  and
E. Cillari
S. Milano
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
F. Arcoleo
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
M. Dieli
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
R. D'agostino
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
G. De Nucci
Affiliation:
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, PO Box 6111, 13081 Campinas, S.P., Brasil
P. D'agostino
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
E. Cillari
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
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Summary

Ex vivo culture of spleen cells from BALB/c mice infected with 2 × 106Leishmania major (L.major) promastigotes were cultured with ConcanavalinA (ConA) or leishmanial antigen (L. Ag) and tested for prostaglandin E2 (PGE2) and for leukotriene B4 (LTB4), in order to study their involvement in the evolution of cutaneous leishmaniasis and the connexion with lymphokine-mediated responses. The data were compared with those obtained in BALB/c mice protected against L. major by sublethal irradiation (550 rad; cured mice). In the unprotected BALB/c mice the levels of PGE2 that were responsible for the depression of interferon-γ (IFN-γ) and tumour necrosis factor-α (TNFα) Th1-associated cytokines and for the relative increase in the interleukin-4 (IL-4) became higher and higher as the lesion progressed. On the contrary, the cured mice produced levels of PGE2 similar to normal uninfected controls, high levels of TNFα and IFN-γ and low levels of IL-4. Elevated levels of LTB4 were detected in the early stage of infection in the unprotected mice compared to cured ones, a sign of more intense inflammation and a stimulus for the recruitment of inflammatory cells. The observation that exogenous LTB4 was able to enhance in vitro both Th1 cytokines in cured mice and Th2 cytokines in unprotected ones suggests that LTB4 could act in the recruitment of the T cells already committed to Th1 or Th2 phenotype.

Keywords

Leishmania majorTNFαIFN-γPGE2LTB4
Type
Research Article
Information
Parasitology , Volume 112 , Issue 1 , January 1996 , pp. 13 - 19
Copyright
Copyright © Cambridge University Press 1996

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