317 INTRODUCTION Mycobacterial infections, particularly tuberculosis (TB), have become a leading global health threat (Bloom & Murray, 1992; Cooper & Flynn, 1995). WHO considers tu- berculosis as global emergency. Incomplete understanding of the nature of protective inflammatory responses and contributing soluble molecules has hampered the development of effective vaccines and therapies (Wakeham et al., 1998). Immunity to mycobacterial infection involves the induction of a cell-mediated immune response, whereby IFN- γ-producing T cells activate the anti-bacterial defense mechanisms of infected macrophages to destroy, or at least contain, mycobacterial growth (Cooper et al., 1993; Orme & Cooper, 1999). IFN-γ, produced primarily by T cells and NK cells, plays a role in anti-mycobacterial immune responses by activating macrophages (Wakeham et al.). Inflammatory response, induced by chronic presence of the mycobacterium in the tissue, is characterized by granuloma, a distinctive pattern of chronic inflammatory reaction (Robbins, 1999). Granulomatous formations, that surround infected cells and caseous necrosis, are an evidence of cellular response against mycobacteria infection. The granulomas formation and modulation are determinant for disease progression, i.e. latency or active disease. Thus, granuloma size and structure may play a role to the outcome of infection (Dannenberg & Rook, 1994). Int. J. Morphol., 23(4):317-322, 2005. Morphometric Analysis of Granulomas Induced by Mycobacterium bovis Suggests an Influence of IFN-Gamma on the Generation and Modulation upon Granulomatous Inflammatory Response in the Different Tissues El Análisis Morfométrico de Granulomas Inducidos por Mycobacterium bovis Sugiere la Influencia del IFN-Gamma en la Generación y Modulación de la Respuesta Inflamatoria Granulomatosa en Diferentes Tejidos *,** Tonya Azevedo Duarte; * Aryon de Almeida Barbosa Jr. & *,*** Sergio Arruda DUARTE, A. T.; BARBOSA JR., A. A. & ARRUDA, S. A morphometric analysis of granulomas induced by Mycobacterium bovis suggests an influence of IFN-Gamma on the generation and modulation upon granulomatous inflammatory response in the different tissues. Int. J. Morphol., 23(4):317-322, 2005. SUMMARY: There is evidence in both human and experimental infection caused by Mycobacterium tuberculosis, that immunologic factors influence susceptibility to infection and the progress of the disease. The present study aims to evaluate the role of IFN- γ upon inflammatory granulomatous response against M. bovis. To pursue that, C57BL/6 mice lacking the genes for synthesis of IFN- γ (IFN-γ -/- ) and their wild-type counterparts (IFN-γ +/+ ) were intravenously inoculated with M. bovis. The ability of M. bovis to survive and replicate in the liver and lungs was evaluated by counting colony-forming unit (CFU). The histopathological features of granulomatous inflammatory response in the liver and lungs were analyzed during the infection by M. bovis. Granuloma parameters such as, size (sectional area), granuloma volume, volume density, and numerical density were calculated in each point of infection. Bacillary load was higher in both organs of the animals that were IFN-γ -/- than in IFN-γ +/+ mice. Granulomas were observed in the IFN- γ -/- mice after 30 days of infection and were detected earlier in controls (15 days of infection). Hepatic granulomas persisted in the IFN- γ -/- mice, but in the IFN-γ +/+ mice control of the inflammation. In conclusion, IFN-γ influenced the multiplication of M. bovis, as well as modulated the granulomatous inflammation. KEY WORDS: Morphometry; Mycobacterium; Tuberculosis; IFN-g; Granuloma. * Centro de Pesquisa Gonçalo Moniz / FIOCRUZ, Salvador – Bahia, Brazil. ** Instituto de Ciências da Saúde, UFBA Salvador – Bahia, Brazil. *** Escola Bahiana de Medicina e Saúde Pública.