Infliximab does not lead to reduction in the interferon-gamma and lymphoproliferative responses of patients with moderate to severe psoriasis.

Treatment of patients with immune-mediated inflammatory diseases with anti-tumour necrosis factor (anti-TNF) agents increases the risk of tuberculosis reactivation, suggesting that it may affect their cellular immune responses. We evaluated cellular immune responses of 12 severe psoriasis patients before and during infliximab treatment. Peripheral blood mononuclear cells were stimulated with phytohaemagglutinin, the superantigen enterotoxin B (SEB), a cytomegalovirus lysate (CMV), and Mycobacterium tuberculosis (Mtb) antigens. The lymphocyte proliferative and IFN-γ responses were evaluated. Treatment with infliximab did not lead to reduction in the IFN-γ and lymphoproliferative responses: it rather increased the overnight release of IFN-γ in phytohaemagglutinin and SEB stimulated cultures. This effect was most noted at the peak of the anti-TNF clinical effect and less prominent at its nadir. Immunoreactivity to CMV was also either unaffected or slightly increased by the anti-TNF. Of note, the IFN-γ and proliferative responses to Mtb by the two tuberculin skin test-reactors were also increased at the peak of infliximab, declining at its nadir. The deleterious consequences of TNF blockade in severe psoriasis patients undergoing infliximab treatment are apparently attenuated by the abbreviation of the immunosuppressive effect of TNF overexpression.

Preventing or reversing immunosenescence: can exercise be an immunotherapy?

There is now a strong body of evidence demonstrating that aging is accompanied by severe alterations in the immune system, a process known as immunosenescence. Among these changes are alterations in T-cell subpopulation size, cytokine secretion pattern, cell replicative capacity and antibody production, all of which culminate in a proinflammatory state called 'inflammaging' and a diminished capacity to respond to new antigens. These alterations are closely related to the increased mortality and morbidity rates observed in this population. However, the role of exercise on the prevention or treatment of immunosenescence is virtually unknown. Data gathered from the literature regarding the effects of physical activity on immune system aging are still limited and conflicting, with existing reports either advocating benefits or asserting a lack of evidence. Exercise as part of a healthy lifestyle has already been shown to provide long-term benefits with regard to cardiovascular, cognitive, psychosocial and other aspects of the elderly. If positive effects are also observed for immunosenescence, exercise could be a highly cost-effective measure to improve human quality of life compared with other strategies currently being pursued.

Anti-TNF-α agents in the treatment of immune-mediated inflammatory diseases: mechanisms of action and pitfalls.

TNF-α is a potent inducer of the inflammatory response, a key regulator of innate immunity and plays an important role in the regulation of Th1 immune responses against intracellular bacteria and certain viral infections. However, dysregulated TNF can also contribute to numerous pathological situations. These include immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis and severe chronic plaque psoriasis. Animal and human studies concerning the role of TNF-α in IMIDs have led to the development of a therapy based on TNF blockage. This article focuses first on the potential mechanisms by which the three currently licensed agents, adalimumab, etarnecept and infliximab, decrease the inflammatory activity of patients with different IMIDs. Second, it focuses on the risks, precautions and complications of the use of TNF-α inhibitors in these patients.

Decrease in Mycobacterium tuberculosis specific immune responses in patients with untreated psoriasis living in a tuberculosis endemic area.

Tuberculosis has emerged as a major concern in patients with immuno-mediated diseases, including psoriasis, undergoing treatment with biologicals. However, it is not known whether the chronically activated immune system of psoriasis patients interferes with their Mycobacterium tuberculosis (Mtb)-specific immunity, especially in tuberculosis-endemic areas like Brazil. We evaluated T-cell responses to a Mtb lysate and to the recombinant Mtb proteins ESAT-6 and Ag85B of tuberculin skin test (TST) positive and TST negative patients with severe or mild/moderate, untreated psoriasis in three different assays: lymphocyte proliferation, enzyme immunoassay for interferon (IFN)-gamma and interleukin (IL)-10 production by peripheral blood mononuclear cells and overnight enzyme immunospot (ELISpot) for enumerating IFN-gamma-secreting cells. In our cohort, a low proportion (29%) of the severe psoriasis patients tested were TST-positive. IFN-gamma and IL-10 secretion and T-cell proliferation to Mtb antigens were reduced in TST-negative but not in TST-positive patients with severe psoriasis when compared to healthy controls with the same TST status. Similarly, severe psoriasis patients had decreased cytokine secretion and proliferative response to phytohemagglutinin. However, most psoriasis patients and healthy controls showed detectable numbers of IFN-gamma-secreting effector-memory T-cells in response to Mtb antigens by ELISpot. TST-negative, mild/moderate psoriasis patients had responses that were mostly intermediary between TST-negative controls and severe psoriasis patients. Thus, patients with severe psoriasis possess decreased anti-Mtb central memory T-cell responses, which may lead to false-negative results in the diagnosis of TB infection, but retain T-cell memory-effector activity against Mtb antigens. We hypothesize that the latter may confer some protection against tuberculosis reactivation.

Deficient in vitro anti-mycobacterial immunity despite successful long-term highly active antiretroviral therapy in HIV-infected patients with past history of tuberculosis infection or disease.

We evaluated the anti-Mycobacterium tuberculosis (Mtb) immune responses of HIV patients after long-term successful HAART, presenting >500 TCD4+ cells/microl, undetectable viral load, and past history of tuberculosis infection (HIV+PPD+, n=14) or disease (HIV+CTB, n=17). Their lymphoproliferative and IFN-gamma responses were compared with those from HIV-uninfected controls either PPD+ (HIV-PPD+, n=17) or with past history of pulmonary tuberculosis (n=15). Most HIV-infected patients presented normal PHA responses while responses to the Mtb recombinant polypeptides ESAT-6 and Ag85B were markedly reduced. Responses to a whole Mtb lysate (S-Mtb) in HIV+PPD+ patients were lower than in HIV-PPD+ controls, while in HIV+CTB patients these responses were similar to that of past-tuberculosis controls. Comparison between the two HIV groups also suggested better S-Mtb responses in those cured from tuberculosis. Thus, while immune responses to single Mtb proteins are depressed even after successful HAART, reactivity to S-Mtb is high, specially in those cured from tuberculosis, possibly as a result of the survival of higher numbers of mycobacteria-specific T cell clones during the immunosuppression phase, which may afford sufficient protection against new Mtb challenges.