Bioimmunotherapy with Recombinant Mouse Granulocyte-Macrophage Colony-Stimulating Factor (Rm GM-CSF) and Melatonin against Experimental Visceral Leishmaniasis
Posted: 11 Feb 2020
Date Written: February 7, 2020
Visceral leishmaniasis (VL) is a neglected tropical protozoan parasitic disease with 20000–30000 death toll. The emergence of drug resistant parasites, serious adverse effects of current anti-leishmanials, and absence of an effective vector control measures and vaccine(s) against VL poses a serious problem to VL treatment and control. In such a scenario, bioimmunotherapy of VL appears to be a promising alternative approach. Here, we have reported the bioimmunotherapeutic effect of recombinant mouse granulocyte-macrophage colony-stimulating factor (rm GM-CSF) and melatonin, a neurohormone against L. donovani-infected BALB/c mice. Co-treatment with rm GM-CSF (10 µg/kg) and melatonin (5 mg/kg) supressed the liver (98.12%) and spleen (96.1%) parasite burden in L. donovani-infected mice compared to monotherapy with rm GM-CSF/melatonin treatment alone. In in vitro, co-treatment with rm GM-CSF (3.2 ng/ml) and melatonin (30 nM) has shown maximum inhibition of intra-cellular amastigote growth than individual treatments of rm GM-CSF and melatonin. In both in vitro and in vivo the combined bioimmunothearapeutic effect of rm GM-CSF and melatonin was annulled by the treatment of anti rm GM-CSF antibody and luzindole, a selective melatonin receptor blocker. Total circulating leukocytes and pool-size peritoneal macrophages (PM) were significantly (P< 0.001) increased in rm GM-CSF (10 µg/kg) and melatonin (5 mg/kg) co-treated L. donovani-infected BALB/c mice compared to negative control. The splenocytes from protected mice and rm GM-CSF (3.2 ng/ml) and melatonin (30 nM) co-treated L. donovani-infected PM, significantly (P<0.001) enhanced the nitrite levels in the culture supernatants. Bone marrow (BM) cellularity was increased and BM infection was completely cleared in protected mice. It is thus concluded that co-treatment with rm GM-CSF and melatonin can protect the VL infected mice and thus warrants further evaluation in primates and human VL.
Keywords: Bioimmunotherapy, Recombinant mouse granulocyte-macrophage colony-stimulating factor, Melatonin, Visceral leishmaniasis
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