Natural killer cell activity, lymphocyte proliferation, and cytokine profile in tumor-bearing mice treated with MAPA, a magnesium aggregated polymer from Aspergillus oryzae.
The present study examined the effects of MAPA, an antitumor aggregated polymer of protein magnesium ammonium phospholinoleate-palmitoleate anhydride, isolated from Aspergillus oryzae, on concanavalin A (Con A)-induced spleen cell proliferation, cytokine production and on natural killer (NK) cell activity in Ehrlich ascites tumor-bearing mice. The Ehrlich ascites tumor (EAT) growth led to diminished mitogen-induced expansion of spleen cell populations and total NK activity. This was accompanied by striking spleen enlargement, with a marked increase in total cell counts. Moreover, a substantial enhancement in IL-10 levels, paralleled by a significant decrease in IL-2 was observed, while production of IL-4 and interferon-gamma (IFN-gamma) was not altered. Treatment of mice with 5 mg/kg MAPA for 7 days promoted spleen cell proliferation, IL-2 production and NK cell activity regardless of tumor outgrowth. In addition, MAPA treatment markedly enhanced IFN-gamma levels and reduced IL-10 production relative to EAT mice. A 35% reduction in splenomegaly with normal number of nucleated cells was also found. Altogether, our results suggest that MAPA directly and/or indirectly modulates immune cell activity, and probably disengages tumor-induced suppression of these responses. Clearly, MAPA has an impact and may delay tumor outgrowth through immunotherapeutic mechanisms.
Justo
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GZ
Departamento de Farmacologia and Hemocentro, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
Durán
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Queiroz
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ML
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001236:Aspergillus oryzae / Q000737:chemistry; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008041:Linoleic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013163:Splenomegaly / Q000276:immunology / Q000517:prevention & control; D013997:Time Factors; D019139:Tumor Escape / Q000187:drug effects
D000970:Antineoplastic Agents; D016207:Cytokines; D008041:Linoleic Acids; D008934:Mitogens; D009943:Organophosphorus Compounds; C076534:magnesium ammonium phospholinoleate anhydride; D003208:Concanavalin A