Chlamydia pneumoniae antibodies associated with altered serum lipid profile.

Chronic Chlamydia pneumoniae infection has been associated with atherosclerosis by seroepidemiological studies. Further, acute bacterial infections are known to influence lipid metabolism. To clarify the possible pathogenetic mechanisms of this association, we studied serum lipids and the C. pneumoniae IgG antibody titers of 1,053 males who participated in the reindeer herders health survey in Northern Finland in 1986-1989. The mean age of the study group was 47 years (range 20-87). When comparing nonsmoking C. pneumoniae antibody-positive (IgG > or = 32) subjects to those with no antibodies, the age-adjusted mean concentration of triglycerides was increased (1.34 vs. 1.04 mmol/l; p = 0.03) and high-density lipoprotein (HDL) was decreased (1.24 vs. 1.35 mmol/l; p < 0.001). HDL:total cholesterol ratio was also decreased (0.20 vs. 0.23; p = 0.01). In smokers changes were very similar, but not statistically significant. Thus, C. pneumoniae antibodies seem to correlate with an altered serum lipid profile considered to increase the risk of atherosclerosis. This finding supports the proposal that infections, in this case C. pneumoniae infection, may play a role in the pathogenesis of atherosclerosis.

Serological evidence of an association between Chlamydia pneumoniae infection and lung cancer.

Epidemiological evidence suggests that airway obstruction is an independent risk factor for lung cancer and that this cannot be explained by active or passive smoking alone. Chlamydia pneumoniae infection has been associated with chronic bronchitis and its exacerbates. Our aim was to evaluate the association between chronic C. pneumoniae infection and risk of lung cancer among male smokers. Smoking males with lung cancer (n = 230) and their age- and locality-matched controls were selected among participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The presence of C. pneumoniae infection was assessed by analyzing specific antibodies and immune complexes in 2 serum samples collected with a 3-year interval before the lung cancer diagnosis. The diagnosis of chronic infection was based on stable levels of positive specific IgA antibody (titer > or = 16) and immune complex (titer > or = 4). Relative risks were estimated by odds ratios (OR) adjusted for age, locality and smoking history by a conditional logistic regression model. Markers suggesting chronic C. pneumoniae infection were present in 52% of cases and 45% of controls and hence were positively associated with the incidence of lung cancer (OR 1.6; 95% confidence interval [CI] 1.0-2.3). The incidence was especially increased in men younger than 60 years (OR 2.9; 95% CI 1.5-5.4) but not in the older age group (OR 0.9; 95% CI 0.5-1.6). Before concluding that C. pneumoniae infection is a new independent risk factor for lung cancer, corroboration from other studies with larger number of cases and longer follow-up is needed.

Chlamydia pneumoniae and chronic lung diseases.

Chlamydia pneumoniae infection has been implicated in several chronic lung diseases by serology and direct antigen detection. Acute lower respiratory tract infection caused by C. pneumoniae seems often to precede attacks of asthma in both children and adults. Chlamydia pneumoniae is also involved in some exacerbations of chronic bronchitis and chronic obstructive lung disease but, more importantly, seems to be strongly associated with the latter irrespective of exacerbation status. Moreover, persistently elevated C. pneumoniae antibody titres have been observed in sarcoidosis and lung cancer.

Reactivation of Chlamydia pneumoniae infection in mice by cortisone treatment.

Reactivation of Chlamydia pneumoniae infection was studied by inducing immunosuppression by cortisone acetate treatment given every other day for 14 days in intranasally infected NIH/s mice. The treatment started 2 or 4 weeks after primary infection, when no C. pneumoniae was detected. C. pneumoniae could be recovered from the lung cultures on days 7 and 9 in 10 and 60% of the mice, respectively, when cortisone treatment was begun 30 days after infection. These results confirm the persistent nature of C. pneumoniae infection.

Experimental Chlamydia pneumoniae infection in mice: effect of reinfection and passive immunization.

NIH/S mice were infected intranasally with Chlamydia pneumoniae isolate Kajaani 6 and rechallenged after either 28 or 70 days. A partial resistance to reinfection, indicated by a reduced recovery of live organisms, was noted at both time points of rechallenge: positive isolations from lung homogenates and/or bronchoalveolar lavage fluids were observed in fewer mice and the yields of isolated chlamydiae remained smaller, as compared to primary infection. However, a previous infection did not confer any protection against inflammatory changes. A strong peribronchial and perivascular inflammation with infiltrating lymphocytes and plasma cells was noted in the lungs of primary infected, as well as reinfected, mice. The effect of passive immunization was also studied. When mice were given convalescent or hyperimmune sera intraperitoneally before inoculation, lower C. pneumoniae isolation yields were detected. As in the rechallenge experiment, marked inflammation could still be seen in the lungs, now with polymorphonuclear leukocyte infiltration. The results suggest that immunological reactions play a role in the pathogenesis of C. pneumoniae infection. Antibodies may be important in reducing the amount of infective elementary bodies, but complete clearing of C. pneumoniae could not be achieved in these experiments, even less a protection against inflammatory lung changes.

Experimental infection of Chlamydia pneumoniae in mice.

NIH/S, Swiss Webster, and BALB/c mice were infected intranasally with three Chlamydia pneumoniae isolates, Kajaani 6, Helsinki 12, and TW-183. C. pneumoniae could be isolated from the lung homogenates and bronchoalveolar lavage fluids up to the third week post-infection. Specific serum IgG antibodies against C. pneumoniae reached high levels in the third week and remained elevated until the end of the 6-week follow-up period. Serum IgM levels were highest in the third week post-infection and started to decrease thereafter. In spite of these signs of ongoing infection, the mice did not show any symptoms of disease. NIH/S mice could be readily and uniformly infected, while BALB/c mice were the most resistant and developed the weakest antibody response. The greatest histological changes were detected in NIH/S mice as well. The inflammatory infiltrate, which consisted of lymphocytes and plasma cells throughout the study, was restricted to the peribronchial and perivascular space and to the interstitium of the lung parenchyma.

Immobilization induces carbonic anhydrase III in type II fibers of rat skeletal muscle.

The amount and fiber distribution of carbonic anhydrase III (CA III), a major soluble protein in Type I muscle fibers, were studied during cast immobilization of rat hindlimb with the ankle in plantar or dorsiflexion. The concentration of CA III increased two- (p less than 0.05) and three- (p less than 0.01) fold in the shortened and lengthened tibialis anterior muscle during a 3-weeks immobilization period, respectively. After 6 weeks of immobilization the increase was even greater (p less than 0.001). Concomitantly, the number of CA III positive fibers in the lengthened muscle increased so that almost all fibers were positive. In the soleus muscle no significant change in the CA III concentration was seen. On the basis of actomyosin ATPase staining, the transition of Type IIb fibers towards Type IIa occurred in the tibialis anterior muscle, whereas in the soleus muscle a transformation of Type I fibers towards Type IIa fibers occurred. Therefore, the increase in the muscle CA III concentration seems to be associated with a cell transformation of the muscle towards a more oxidative type.

Consecutive expression of carbonic anhydrase isoenzymes during development of rat liver and skeletal muscle differentiation.

The appearance of carbonic anhydrase isoenzymes in rat liver and skeletal muscle during fetal and postnatal development was studied with immunohistochemistry. In the 12-day fetus the early strong expression of CA I in hepatocytes was partially replaced by the expression of CA II and CA III during late prenatal development. In the 20-day fetus the staining intensity of CA III was equal to that of a mature female rat. In the male, the staining intensity in hepatocytes clearly increased during sexual maturation. Immunoelectron microscopy showed diffuse cytoplasmic and nucleoplasmic staining of CA III in hepatocytes. The time-dependent expression of the isoenzymes in hepatocytes may reflect a different metabolic function of these structurally closely related isoenzymes. In skeletal muscle, CA III was the only isoenzyme detected during development. In late prenatal and early postnatal stages all muscle fibers contained about equal amounts of CA III. The differentiation of the muscle according to the expression of CA III occurred during the first 3 postnatal weeks.