Immunomodulatory Properties

The effects of neem on the immune system are complex and have not been fully elucidated; some evidence points to an immunostimulant effect, while other evidence suggests it can also act as an anti-inflammatory. The latter may be partly explained by inhibition of prostaglandin synthetase (Van der Nat et al., 1991; Okpanyi and Ezeukwu, 1981; Obaseki et al., 1985). However, Kroes et al. (1993) showed that in a classical Ayurvedic preparation for gout, nimba arishta, the anti-inflammatory activity is almost entirely attributable to ingredients other than neem.

Here we review the evidence for the immunostimulant effects of neem, and to what extent this may explain its perceived efficacy in the treatment of malaria. There is a small amount of evidence that neem may boost both the humoral and the cell-mediated immune responses to malarial infection, but it comes mostly from mice, which may have different immune responses from man, and in which neem has not been shown effective against malaria.

6.2.3.3.1 Humoral Immunity

Patients who produce specific antimalarial immunoglobulins M (IgM) and G (IgG) present with lower p. falciparum parasitaemia and are less likely to have recrudescent infections (Mayxay et al., 2001). IgG also protects newborns against malaria, following passive transfer across the placenta (Marsh, 1993). Ray et al. (1996) showed that mice fed on A. indica leaf extracts (in peanut oil) produced more IgM and IgG than controls in response to challenge with ovalbumin, and this effect was dose related. In rats and mice, production of antibodies in response to challenge with sheep red blood cells is increased after intraperitoneal injection of 100 mg/kg of aqueous neem bark or leaf extract, and immunosuppression due to stress was reduced (Sen et al., 1992; Njiro and Kofi-Tsekpo, 1999).

6.2.3.3.2 Cell-Mediated Immunity

Cytotoxic T cells and interferon-g (IFN-g) can eliminate intracellular plasmodia in hepatocytes and erythrocytes, and macrophages may also play a role (Plebanski and Hill, 2000). Neem seed oil injected intraperitoneally in mice induces the production of IFN-g by spleen cells (Upadhyay et al., 1992). It also increases peritoneal leukocyte counts, enhances the phagocytic activity of macrophages, enhances the lymphocyte proliferative response to in vitro mitogen challenge, and enhances the cellular immune response to tetanus toxoid.

However, in vitro, a neem bark decoction reduced the phagocytic activity of neutrophils, but stimulated the production of migration inhibition factor (MIF) by human lymphocytes (Van der Nat et al., 1987). MIF attaches macrophages and monocytes to their site of action. Indeed, in mice, Ray et al. (1996) found that macrophage migration is inhibited by 100 mg/kg of neem leaf extract; however, in contradiction to this finding, Sen et al. (1992) found that aqueous neem leaf extract promotes leukocyte migration in rats.

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