Olobo JO, Geletu M, Demissie A, Eguale T, Hiwot K, Aderaye G, Britton S. Circulating TNF-a, TGF-b, and IL-10 in Tuberculosis Patients and Healthy Contacts. Scand J Immunol 2001;53:85-91 Levels of tumour necrosis factor (TNF)-a, transforming growth factor (TGF)-b, and interleukin (IL)-10 in plasma of pulmonary tuberculosis (TB) patients and healthy contacts and plasma and pleural fluid of patients with tuberculous pleuritis were examined by enzyme immunoassay. Plasma TNF-a and IL-10 were elevated to significant levels in healthy contacts. High levels of TGF-b and IL-10 were also detected in plasma from TB patients and healthy contacts. Pleural fluid contained all three cytokines with the level of IL-10 being highest followed by TGF-b and TNF-a. Plasma of tuberculous pleuritis patients also had detectable levels of the three cytokines. Increased levels of TNF-a in plasma of contacts and to some extent pleural fluid of pleuritis patients, is perhaps to limit the infection, while elevated IL-10 in plasma of TB patients and contacts and pleural fluid would perhaps modulate excess proinflammation. Elevated TGF-b in TB patients suggests its role in the immunopathogenesis.

We examined the immune responses of patients with active pulmonary tuberculosis (TB) and their healthy household contacts to short-term culture filtrate (ST-CF) of Mycobacterium tuberculosis or molecular mass fractions derived from it. Our goal was to identify fractions strongly recognized by donors and differences among the donor groups of possible relevance for vaccine development. The study population consisted of 65 human immunodeficiency virus-negative donors from the Hossana Regional Hospital, Hossana, Ethiopia. Peripheral blood leukocytes from the donors were stimulated with different antigens and immune responses were determined. Household contacts produced significantly higher levels of gamma interferon (IFN-γ) than the TB patients in response to antigens present in ST-CF and the 10 narrow-molecular-mass fractions. A similar difference in leukocyte proliferative responses to the antigens between the two groups was also found. In general, while all fractions stimulated immune responses, the highest activity was seen with the low-molecular-mass fractions, which include well-defined TB antigens such as ESAT-6. Leukocytes from contacts of TB patients with severe disease produced higher levels of antigen-specific IFN-γ than those from contacts of patients with minimal disease. Both groups of contacts exhibited higher cell-mediated responses than the patients themselves. The enhanced immune response of healthy contacts, especially those of patients with severe disease, to secreted mycobacterial antigens is suggestive of an early stage of infection by M. tuberculosis, which could in time result in overt disease or containment of the infection. This possibility is currently being investigated by follow-up studies of the household contacts.