TNF-α treatment induced a decrease in TNF-α, IL-12p40 and IL-10 mRNA levels in peritoneal cells following PPD stimulation while live M. tuberculosis caused an increase in TNF-α mRNA and a decrease in the IL-10 mRNA expression. TNF-α injection also induced an increase in the infiltration of mononuclear cells and in the proportions of CD3+ T cells in the lymph nodes. These see more results indicate that rgpTNF-α enhances some aspects of T cell immunity and promotes control of mycobacteria in the tissues. Future studies will address the role of TNF-α in BCG-vaccinated guinea pigs following low-dose pulmonary challenge with virulent M. tuberculosis. Among the many cytokines that contribute to a protective immune

response against Mycobacterium tuberculosis, tumour necrosis factor (TNF)-α is known to play an essential role in the formation and maintenance of granulomas [1,2]. Resistance against M. tuberculosis

is mediated by T cells and macrophages [3–5]. Several cytokines, including interleukin (IL)-12, IL-17 and IL-23, contribute to the host-response to mycobacteria by enhancing the development of T helper type 1 (Th1) immunity [6,7]. Among the Th1 cytokines, interferon (IFN)-γ and TNF-α have been identified as the most important players in the cytokine cascade for anti-mycobacterial immunity because the formation as well as the maintenance of the granuloma are mediated by TNF-α, and it synergizes with IFN-γ in activating macrophages for the production of effector molecules [2,8]. It is known that susceptibility to tuberculosis

occurs with defects in the type-1 cytokine pathway in humans [9,10]. The importance selleck kinase inhibitor of IFN-γ has been well established in mouse models, as disruption of IFN-γ, the IFN-γ receptor gene or components of the IFN-γ receptor signal-transducing chain resulted in an exacerbation of disease after M. tuberculosis or M. bovis infection [9,11]. Neutralization of TNF-α in mice resulted the in the reactivation of latent M. tuberculosis infection, disrupted granuloma formation and rapid death [12]. In another study, neutralization of TNF-α resulted in marked disorganization of granulomas and an increase in proinflammatory cytokine and chemokine expression in mice given an aerosol infection with M. tuberculosis[13]. Mice deficient for TNF-α or TNF-R1 showed disruption in granuloma formation and succumbed to infection with M. tuberculosis[14]. The importance of TNF-α in anti-mycobacterial immunity has been reinforced by reports that the use of TNF-α neutralizing antibody in the treatment of chronic inflammatory diseases resulted in the reactivation of latent tuberculosis in humans [15], [10]. Several reports also indicate that injection of mice with recombinant TNF-α or IFN-γ alone or in combination was associated with decreased microbial growth and increased survival after infection with disseminated M. avium complex or M. tuberculosis[16,17].