The relationship between infections and autoimmunity as well as the risk of infections due to antirheumatic agents, including corticosteroids, immunosuppressants and biologics, are discussed. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental factors. This review focuses on the pivotal role of infection in the induction of autoimmune disorders. Although the development of autoimmune phenomena linked to infections is a common finding, the onset of autoimmune diseases is a rare event, arising from a combination of genetic susceptibility and environmental factors. There are several mechanisms through which pathogens can initiate or perpetuate autoimmunity. Some of them are antigen-specific, including molecular mimicry, expression of modified, cryptic, or new antigenic determinants, and superantigens. Others are nonspecific and collectively known as “bystander activation.” They include enhanced processing and presentation of self-antigens, immune cell activation, cytokine release, and cell apoptosis/necrosis. Infections may also trigger organ-specific autoimmune diseases, but studies carried out until now have provided conflicting and inconclusive results regarding the role of viral and bacterial agents. Infections and autoimmune diseases have multifaceted and multidirectional relationships. It has been suggested recently that infections cannot only induce or precipitate autoimmune diseases, but they may also protect from autoimmunity or even abrogate an ongoing autoimmune process depending on the interaction between microorganisms and host. Therefore, we should look at microorganisms, not only as causes of infections but also as potential agents able to modulate the immune system. On the other hand, numerous evidences have emerged regarding the higher susceptibility of autoimmune patients to infections, possibly as a result of immunosuppressive therapy and treatment with biologic agents.

A 49 year old man was diagnosed as having RA in January 1990. HBsAg, and HBe and HBc antibodies were positive, while HBe antigen and HBs antibodies were negative. From January 1990 to May 2000 he received several treatments consisting of different disease modifying antirheumatic drugs (DMARDs) (hydroxychloroquine, sulfasalazine, sodium aurothiomalate, and cyclosporin A) in addition to oral steroids (<10 mg/day of prednisone) and non-steroidal antiinflammatory drugs. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) remained persistently normal. However, response to these treatments was poor, and peripheral arthritis persisted. In June 2000 he began treatment with infliximab (6 mg/kg every eight weeks) associated with methotrexate (10 mg/week), with a good response of the joint signs and symptoms, as well as the inflammatory indices. In January 2002 he developed malaise, anorexia, fatigue, increased levels of AST (97 IU/l) and ALT (176 IU/l), and then he was admitted to our division.

Rationale: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung, yet the mechanisms that regulate this immune-inflammatory response are not fully understood. Objectives: We investigated whether IL-32, a newly discovered cytokine, was related to markers of inflammation and clinical progression in COPD. Methods: Using immunohistochemistry, expression of IL-32 was examined in surgically resected specimens from 40 smokers with COPD (FEV₁ = 39 ± 4% predicted), 11 smokers with normal lung function, and 9 nonsmoking control subjects. IL-32 was quantified in alveolar macrophages, alveolar walls, bronchioles, and arterioles, and confirmed by molecular analysis. The levels of IL-32 were correlated with the cellular infiltrates, markers of inflammation, and clinical data. Measurements and Main Results: Macrophage staining for IL-32 was increased in smokers with COPD compared with control smokers and nonsmokers (P = 0.0014 and P < 0.0001, respectively), and similar differences were observed in alveolar walls (P = 0.0004 and P = 0.0005) and bronchiolar epithelium (P = 0.004 and P = 0.0009). This increase was also detected at the mRNA level (P = 0.007 vs. control smokers and P = 0.029 vs. nonsmokers) and was mainly due to non-α isoforms. Moreover, IL-32 expression was positively correlated with tumor necrosis factor-α (P = 0.004, r_s=0.70), CD8⁺cells (P = 0.02, r_s=0.46), phospho p38MAPK (P < 0.01, r_s=0.60) and negatively with FEV₁ values (P = 0.004, r_s= −0.53). Conclusions: This is the first study to demonstrate increased expression of IL-32 in lung tissue of patients with COPD, where it was colocalized with tumor necrosis factor-α and correlated with the degree of airflow obstruction. These results suggest that IL-32 is implicated in the characteristic immune response of COPD, with a possible impact on disease progression.

Objective: To determine the effect of tumour necrosis factor α (TNFα) blockade with etanercept in refractory knee joint synovitis (KJS) in rheumatoid and psoriatic arthritis, by local and systemic disease activity assessment and combined grey scale and power Doppler ultrasonographic monitoring. Methods: 27 knees affected by rheumatoid KJS (n = 12) and psoriatic KJS (n = 8) were assessed before receiving treatment and at 3 and 12 months’ follow up. Time dependent clinical changes in disease activity were monitored by C reactive protein, erythrocyte sedimentation rate (ESR), global health status (GHS), and Ritchie (RAI) and knee joint articular (KJAI) indices; synovial changes were monitored by ultrasonographic and power Doppler indices for grey scale synovial thickening and for distinct intrasynovial vessel power Doppler flow configurations (fluid/synovium interface (F/SI-PD) and pannus/cartilage interface (P/CI-PD)). Interobserver and intraobserver variability of grey scale and power Doppler ultrasonographic was evaluated. Response to treatment was assessed by analysis of variance for repeated measures on clinical and ultrasonographic variables. Results: Rapid (3 months) reduction in F/SI-PD flow (p<0.001), parallel to reductions of C reactive protein (p<0.05), ESR (p<0.001), KJAI (p<0.002), RAI, and GHS (p<0.001), was sustained at 12 months when it was accompanied by reduction in both synovial thickening and P/CI-PD flow (p<0.001). No differences (ANOVA) were noted at baseline or at 12 months in clinical and ultrasonographic variables between either the rheumatoid or the psoriatic KJS groups. Conclusion: Grey scale and power Doppler ultrasonography are reliable measures of long term change in rheumatoid and psoriatic KJS disease activity in response to anti-TNFα treatment with etanercept.