CYTOKINE PATTERNS IN TUBERCULOUS AND SARCOID GRANULOMAS - CORRELATIONS WITH HISTOPATHOLOGIC FEATURES OF THE GRANULOMATOUS RESPONSE

Cytokines play an important role in granuloma formation, but the exten t that cytokine profiles are similar in different granulomatous diseas es and whether differences in the histopathologic features of the gran ulomatous response results from differences in cytokine production hav e not been evaluated. To investigate these questions, we used RT-PCR t o quantify the expression of mRNAs coding for 16 cytokines in granulom atous lymph nodes from patients with tuberculosis and sarcoidosis and from control tissues, and we sought correlations between the level of expression of these cytokines and the histopathologic features of the granulomas. Expression of mRNAs coding for a number of cytokines (IL-1 beta, IFN-gamma, TNF-alpha, granulocyte-macrophage (GM)-CSF, IL-12 (p 40), and lymphotoxin-beta) was increased in tuberculous and sarcoid gr anulomas compared with that of control tissues. All sarcoid granulomas were shown to express a Th1 pattern of cytokine mRNAs, while tubercul ous lymph nodes expressed either a Th1 or a Th0 profile. CM-CSF and ly mphotoxin-beta mRNAs were more abundant in sarcoid than in tuberculous granulomas, whereas IL-8 mRNA was strongly expressed only in tubercul ous lymph nodes. Strong expression of GM-CSF, TNF-alpha, and IL-8 by g ranulomas was shown to be correlated, respectively, with the presence of florid granulomatous lesions, the absence of central necrosis, and the presence of neutrophil infiltration. These results demonstrate tha t the formation of tuberculous and sarcoid granulomas in humans is ass ociated with the expression of characteristic cytokine profiles and in dicate that the expression of certain cytokines is associated with the development of specific pathologic features in the resulting granulom as.