Differential effects of anti-inflammatory cytokines (IL-4, IL-10 and IL-13) on tumoricidal and chemotactic properties of human monocytes induced by monocyte chemotactic and activating factor.
The effect of recombinant human IL-4, IL-10, and IL-13 on the chemotaxis and antitumor activity of human blood monocytes induced by monocyte chemotactic and activating factor (MCAF) was examined. MCAF alone did not induce monocyte-mediated cytotoxicity against human melanoma (A375-M) cells whereas it significantly enhanced the cytotoxicity by norMDP-stimulated monocytes. MCAF, unlike IFN-gamma, had no priming effect on monocyte activation by norMDP. MCAF acted with norMDP or LPS to enhance the production of both IL-1 beta and TNF-alpha. Enhanced cytotoxicity of monocytes stimulated with MCAF plus norMDP was reduced by IL-1 receptor antagonist and anti-TNF-alpha antibody. IL-4, IL-10, and IL-13 suppressed the generation of antitumor activity and cytokine production (IL-1 beta and TNF-alpha) of monocytes stimulated with MCAF plus norMDP or LPS. Chemotaxis of monocytes induced by MCAF was not affected by norMDP or any of the anti-inflammatory cytokines (IL-4, IL-10, and IL-13). Moreover, the pretreatment of monocytes with anti-inflammatory cytokines did not suppress monocyte-chemotaxis. These findings suggest that in vivo recruitment and anti-tumor expression of blood monocytes induced by MCAF may be differently regulated by anti-inflammatory cytokines in vivo.
Third Department of Internal Medicine, University of Tokushima School of Medicine, Japan.
S
S
Yano
S
S
Sone
Y
Y
Nishioka
N
N
Mukaida
K
K
Matsushima
T
T
Ogura
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D018793:Interleukin-13; D007378:Interleukins; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C037224:N-acetyl-demethylmuramyl-alanyl-isoglutamine