Chlamydia pneumoniae infection has been associated with asthma and atherosclerosis. Smooth muscle cells represent host cells for chlamydiae during chronic infection. In this study we demonstrated that C. pneumoniae infection of human smooth muscle cells in vitro increased production of interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) as shown by reverse transcription-PCR, immunoblotting, and enzyme-linked immunosorbent assay. In contrast, levels of platelet-derived growth factor A-chain mRNA were not affected after infection. The stimulation of bFGF and IL-6 production was most effective when viable chlamydiae were used as inoculum. Furthermore, inhibition of bacterial protein synthesis with chloramphenicol prevented up-regulation of IL-6 and bFGF in infected cells. Addition of IL-6 antibody to infected cultures diminished bFGF expression, indicating involvement of produced IL-6. These findings suggest that chlamydial infection of smooth muscle cells elicits a cytokine response that may contribute to structural remodeling of the airway wall in chronic asthma and to fibrous plaque formation in atherosclerosis.Chlamydia pneumoniae (in a recent paper renamed Chlamydophila pneumoniae) is an obligate intracellular bacterial pathogen that causes acute respiratory infections (9). Moreover, chronic or recurrent chlamydial infections have been associated with asthma and atherosclerosis. C. pneumoniae has a biphasic growth cycle. Infectious elementary bodies (EBs) enter the host cell and differentiate into reticulate bodies (RBs). These RBs divide by binary fission within the expanding endosome, resulting in development of an intracellular inclusion. After a period of growth, RBs reorganize into new EBs that are released by host cell lysis or exocytosis. Chronic infections are obviously associated with lytic and nonlytic phases in which chlamydiae do not replicate.Evidence for C. pneumoniae in asthma comes from serodiagnostic studies and culture (3,13,14). The association of asthma with elevated specific immunoglobulin G (IgG) antibodies seems to be strongest for nonatopic long-standing asthma (37). These studies suggest an important role for chronic infection as a promoting factor that would produce a tendency to severe chronic asthma. It is possible that chlamydiae amplify the inflammation in patients with early mild asthma, leading to permanent changes in the airways (37). Furthermore, C. pneumoniae can probably initiate adult-onset asthma (15). Activation of a synthetic phenotype of smooth muscle cells (SMC) plays an important role in the pathogenesis of asthma (17). Chronic inflammation and cycles of repair in chronic asthma lead to structural remodeling of the airway wall. This process is characterized by smooth muscle hyperplasia and hypertrophy and by thickening of the basement membrane with deposition of collagen types III and V (31, 33). The increase in the amount of SMC results in an enhanced contractile response and in irreversible airflow obstruction.The pathogenesis of atherosclerosis also invo...

Objective. To investigate the effect of long-term antibiotic treatment in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. Methods. One hundred twenty-six patients were treated with ciprofloxacin (500 mg twice a day) or placebo for 3 months, in a double-blind, randomized study. Of these patients, 104 (48 treated with cipro-floxacin and 56 treated with placebo) were valid for clinical evaluation: 55 were diagnosed as having ReA with a preceding symptomatic urogenic or enteric infection and 49 as having undifferentiated oligoarthritis. These 2 groups were randomized separately. The triggering bacterium was sought by serology and/or culture. The percentage of patients in remission after 3 months of treatment was chosen as the primary efficacy parameter. Results. A triggering bacterium could be identified in 52 patients (50%): Chlamydia trachomatis in 13, Yersinia in 14, and Salmonella in 25. No patient was positive for Campylobacter jejuni or for Shigella. No difference in outcome was found between treatment with ciprofloxacin or placebo in the whole group or in subgroups of patients with ReA or undifferentiated oligoarthritis. No difference was seen in patients with a disease duration <3 months. Ciprofloxacin was not effective in Yersinia-or Salmonella-induced arthritis but seemed to be better than placebo in Chlamydia-induced arthritis. This difference was not significant, however, which might be due to the small sample size. Conclusion. Long-term treatment of ReA with ciprofloxacin is not effective; however, it might be useful in the subgroup of patients who have Chlamydia-induced arthritis. This has to be proven in a bigger study focusing on patients with Chlamydia-induced arthritis.

Conclusions-Chlamydiatrachomatis, yersinia, and salmonella can be identified as the causative pathogen in about 50% of patients with probable or possible ReA if the appropriate tests are used. (Ann Rheum Dis 2001;60:337-343) Reactive arthritis (ReA) is a well known complication of enteric infections caused by yersinia, salmonella, shigella, and campylobacter, or of urogenital tract infections caused by Chlamydia trachomatis.

The seroprevalence of anti-Chlamydia pneumoniae-specific immunoglobulin G (IgG) antibodies is high in the adult population. Experience is required to perform a microimmunofluorescence test (MIF), the current "gold standard" for serological diagnosis, and the assay still lacks standardization. Partially automated enzymelinked immunosorbent assays (ELISAs) and enzyme immunoassays (EIAs), which are more standardized and for which the reading of results is less subjective, have been developed. The different commercially available serological tests differ in their sensitivities and specificities, depending primarily on the antigen used. Therefore, we evaluated 11 different tests (10 were species specific, 1 was genus specific) for IgG antibodies using serum samples of 80 apparently healthy volunteers. The interpretation of the results was based on the results of the gold standard, MIF: a sample was judged positive if it was positive by at least three of the four different MIFs. Based on this internal standard, we found that 71% of the samples were positive, while 8% were false positive by some tests. The correlations between the results of the different MIFs ranged from 83 to 99%, and the correlations between the results of the MIFs and the different ELISAs and EIAs ranged from 78 to 98%. Comparison of the IgG titers measured by MIF showed good agreement (r ‫؍‬ 0.76 to 0.91). This analysis revealed that some ELISAs and EIAs fail to detect low IgG titers. The specificities of the species-specific tests varied from 95 to 100%, and the sensitivities varied from 58 to 100%. These results indicate that serological assays for the detection of anti-C. pneumoniae-specific IgG vary greatly in their sensitivities and specificities. MIF must still be considered the best method for the detection of IgG in apparently healthy subjects, but the sensitivities and specificities of new ELISAs approximate those of MIFs.

Monoclonal antibodies (MAbs) against the virulence-associated Mip protein of Legionella spp. were raised by immunizing BALB/c mice with (i) Legionella pneumophila, (ii) Legionella micdadei, and (iii) purified recombinant native Mip protein cloned from L. pneumophila Philadelphia 1. Following screening of seeded wells by immunoblot analysis with homologous antigens, eight Mip-specific MAbs were found. These MAbs were chosen to investigate the antigenic diversity of Mip proteins in the genus Legionella. Mip was detected in 82 Legionella strains representing all 34 species tested. One of these MAbs, obtained from immunization with L. micdadei, recognized an epitope common to all Legionella species tested by immunoblot analysis. Another MAb was discovered to be specific for the Mip protein of L. pneumophila. The remaining six MAbs recognized 18 to 79% of Legionella species included in this study. By making use of the MAbs introduced in this study, it could be shown that, based on Mip protein epitope expression, Legionella species can be divided into at least six antigenetically distinct groups. As demonstrated by 43 L. pneumophila strains representing all serogroups, no antigenic diversity of Mip proteins was found for this species. In addition, 18 non-Legionella species, including Chlamydia trachomatis, Neisseria meningitidis, Pseudomonas aeruginosa, and Saccharomyces cerevisiae, all of which are known to carry genes homologous to the Legionella mip genes, were reacted against all eight MAbs. No cross-reactivity was detectable in any of those strains.