PMID- 1905642
OWN - NLM
STAT- MEDLINE
DCOM- 19910805
LR  - 20081121
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 21
IP  - 7
DP  - 1991 Jul
TI  - Cytokine interactions in experimental cutaneous leishmaniasis. II. Endogenous 
      tumor necrosis factor-alpha production by macrophages is induced by the 
      synergistic action of interferon (IFN)-gamma and interleukin (IL) 4 and accounts 
      for the antiparasitic effect mediated by IFN-gamma and IL 4.
PG  - 1669-75
AB  - Tumor necrosis factor-alpha (TNF-alpha) strongly activates murine peritoneal 
      macrophages (M phi) for killing of amastigotes from Leishmania major in the 
      presence of low amounts of interferon-gamma (IFN-gamma). Recently, we found that 
      IFN-gamma and interleukin 4 (IL 4) also synergistically enhance the 
      antileishmanial potential of M phi. In this report, evidence is provided that the 
      synergism of IFN-gamma and IL 4 is based on the ability of the lymphokines to 
      induce the endogenous production of TNF-alpha. First, both IFN-gamma and IL 4 as 
      single agents and in combination were potent inducers of TNF-alpha production by 
      M phi infected with L. major amastigotes. Second, the synergistic effect of 
      IFN-gamma and IL 4 on parasite killing by M phi strongly correlated with their 
      synergistic effect on the release of TNF-alpha. Third, the IFN-gamma/IL 
      4-mediated parasite elimination was completely abrogated not only in the presence 
      of antibodies to IFN-gamma and IL 4, but also with an antibody specific for 
      TNF-alpha. Consistent with the conclusion that endogenously produced TNF-alpha 
      accounts for the synergism of IL 4 with IFN-gamma is the finding that N 
      omega-monomethyl-L-arginine, an inhibitor of the L-arginine-dependent generation 
      of microbicidal nitrogen intermediates, totally blocked the M phi activation 
      induced by IFN-gamma combined with IL 4 as well as by IFN-gamma combined with 
      TNF-alpha. These results underline the complex interplay of cytokines derived 
      from lymphocytes and M phi and the role of TNF-alpha as pivotal factor for the 
      induction of antileishmanial effector functions.
FAU - Stenger, S
AU  - Stenger S
AD  - Institute of Clinical Microbiology, University of Erlangen, FRG.
FAU - Solbach, W
AU  - Solbach W
FAU - Rollinghoff, M
AU  - Rollinghoff M
FAU - Bogdan, C
AU  - Bogdan C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 207137-56-2 (Interleukin-4)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Drug Synergism
MH  - Female
MH  - Interferon-gamma/*pharmacology
MH  - Interleukin-4/*pharmacology
MH  - Leishmania tropica/*drug effects
MH  - Leishmaniasis/metabolism/therapy
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
EDAT- 1991/07/01 00:00
MHDA- 1991/07/01 00:01
CRDT- 1991/07/01 00:00
PHST- 1991/07/01 00:00 [pubmed]
PHST- 1991/07/01 00:01 [medline]
PHST- 1991/07/01 00:00 [entrez]
AID - 10.1002/eji.1830210713 [doi]
PST - ppublish
SO  - Eur J Immunol. 1991 Jul;21(7):1669-75. doi: 10.1002/eji.1830210713.