Opsonizing antibodies (IgG1) up-regulate monocyte proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-6 but not anti-inflammatory cytokine IL-10 in mycobacterial antigen-stimulated monocytes-implications for pathogenesis

Cachexia is one of the prominent features of advanced tuberculosis (TB) see n in association with increased expression of the monokine TNF-alpha. Sever al mycobacterial proteins, including PPD, stimulate TNF-alpha secretion fro m monocytes. Host factors that may play a role in cytokine expression from monocytes remain largely unknown. One such factor is the opsonizing antibod ies. Monocytes have high-affinity receptors (Fc gammaI and Fc gamma III) fo r IgG1 and IgG3 antibodies that mediate antigen uptake. We have reported se lective up-regulation of IgG1 (which bind to Fc gamma receptors) in advance d TB and have recently shown the ability of PPD-specific IgG1 antibodies to augment TNF-alpha expression in PPD-stimulated monocytes. These observatio ns have now been extended to other cytokines with semipurified fractions fr om secreted antigens of Mycobacterium tuberculosis (containing 30 kD and 58 kD) that were devoid of lipids, glycolipids and carbohydrates. In the pres ence of heat-inactivated TB plasma containing known amounts of antigen-spec ific IgG1 antibodies, these fractions induced significantly increased TNF-a lpha, IL-6 and IL-10 secretion. Absorption of IgG1 with Protein 'A' removed the augmenting activity for TNF-alpha and IL-6 secretion from the TB plasm a samples. In the case of IL-10, removal of IgG1 resulted in increased rath er than decreased IL-10 secretion. These results suggest a possible pathoge nic role for antibodies in TB by enhancing proinflammatory and blocking dow n-regulatory cytokines such as IL-10 cytokines during the chronic phase of TB.