Association of IL-6 and IL-6R gene polymorphisms with susceptibility to respiratory tract infections in young Finnish men.

Interleukin-1 (IL-6) is an important mediator of inflammatory response in the respiratory tract during an infection, and the action of IL-6 is mediated by an IL-6 receptor. Several polymorphisms in the IL-6 and IL-6R genes have been associated with different inflammatory disease states. We studied the association between 2 IL-6 (IL6A and IL6B) and 5 IL-6R gene polymorphisms (IL6R1 to IL6R5) and respiratory infections in 511 Finnish military recruits whose respiratory infectious episodes were followed during 6 months of service. A promoter polymorphism of the IL-6R gene, IL6R1 (-183G/A), and two intron 1 polymorphisms, IL6R2 (A/G) and IL6R3 (T/A), were associated with infections. The strongest associations were found for the IL6R1 and IL6R2 polymorphisms, which were in the same linkage disequilibrium block. Conscripts with the A/A (IL6R1), G/G (IL6R2), and A/A (IL6R3) genotypes had an increased risk for respiratory infections during service as follows: odds ratio (OR) 1.72, 95% confidence interval (CI) 1.35-2.19; OR 1.66, 95% CI 1.23-2.26; and OR 1.23, 95% CI 0.98-1.55, respectively. IL-6 gene polymorphism IL6A (-174C/G) was associated with infections only in combination with an IL-6R polymorphism. Our data suggest that polymorphisms in the 5' area of the IL-6R gene may be associated with increased susceptibility to respiratory infections.

Pneumococcal carriage is more common in asthmatic than in non-asthmatic young men.

INTRODUCTION: The aim was to investigate the prevalence of oropharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis and beta-haemolytic streptococci among asthmatic and non-asthmatic young Finnish men and to identify putative risk factors. OBJECTIVES: A total of 224 asthmatics and 668 non-asthmatic men (mean age 19.6 years) from two intakes of conscripts to the Kainuu Brigade, Finland in July 2004 and January 2005 were enrolled upon entering military service. METHODS: Oropharyngeal specimens were examined for bacteria by routine culture methods. All the participants filled in questionnaires concerning risk factors for asthma and respiratory infections. RESULTS: S. pneumoniae (48 cases, 5.4%), Group A streptococci (16, 1.8%), H. influenzae (45, 5.0%), M. catarrhalis (24, 2.7%) and N. meningitidis (20, 2.2%) were isolated from the 892 participants. Ten putative risk factors for oropharyngeal colonization (asthma, atopy, allergic rhinitis, smoking, current use of asthma medication, history of adeno/tonsillectomy, level of highly sensitive C-reactive protein, peak expiratory flow, results of a 12-min running test and body mass index) were evaluated. The only significant risk factor for S. pneumoniae carriage was asthma (OR, 2.04; 95% CI 1.12 to 3.72). CONCLUSIONS: Pneumococcal carriage is more common in asthmatic than in non-asthmatic young men.

Quantification of Chlamydia pneumoniae in cultured human macrophages and HL cells: comparison of real-time PCR, immunofluorescence and ELISA methods.

Chlamydia pneumoniae is an intracellular gram-negative bacterium, which replicates only in eukaryotic cells. Quantification of C. pneumoniae in cell culture is needed when studying e.g. the effect of drugs or host cell factors on infectivity and replication. Conventionally, this has been performed by immunofluorescence staining and microscopic counting of chlamydial inclusions. However, this method is usable only if the cell numbers do not fluctuate in cell culture vials and the inclusions are uniform. In macrophages, inclusions are often aberrant, their sizes vary, and multiple inclusions are also seen. Therefore, methods are needed to quantify exact amounts of C. pneumoniae in cells. Here, we describe a new method based on the real-time PCR quantification of chlamydial genomes adjusted to the number of human genomes in cultures. In human epithelial (HL) cell cultures, the C. pneumoniae inclusion numbers and the ratio of C. pneumonia genomes/human genome (Cpn/Hum) correlated significantly (r = 0.978, p < 0.001); thus with HL cells, both methods are usable. However, in macrophage cultures, the correlation was weaker (r = 0.133, p = 0.036) and we recommend PCR quantification for exact measurements.

Smoking status interacts with the association between mannose-binding lectin serum levels and gene polymorphism and the carriage of oropharyngeal bacteria.

Mannose-binding lectin (MBL) role in the carriage of oropharyngeal bacteria is not known. We investigated the association of smoking, MBL2 polymorphisms, and MBL concentrations with oropharyngeal carriage of respiratory bacteria in young men. Oropharyngeal specimens, MBL concentrations, and MBL2 gene polymorphisms were measured in 124 asthmatic and 394 nonasthmatic Finnish military recruits. The carriage rates of S. pneumoniae (p = 0.002), N. meningitidis (p = 0.005), and beta-hemolytic streptococci (p < 0.001) throughout the military service were significantly higher among smokers than in nonsmokers. An MBL level below the median proved to be a significant risk factor for the carriage of N. meningitidis (odds ratio [OR] = 1.9; 95% confidence interval [CI] 1.0-3.6) and beta-hemolytic streptococci (OR = 2.0; 95% CI 1.2-3.2) in the nonsmokers and a borderline significant risk factor for the carriage of S. pneumoniae (OR = 1.5; 95% CI 0.9-2.6), whereas low MBL levels producing MBL2 haplotypes (LXA/LXA, LXA/O, HYA/O, LYA/O, O/O) seemed to be associated with the carriage of N. meningitidis (OR = 1.8; 95% CI 1.0-3.4) and S. pneumoniae (OR = 1.6; 95% CI 0.9-2.7). Thus, MBL deficiency may predispose nonsmokers to oropharyngeal carriage of these bacteria. We hypothesize that the major factor contributing to elevated bacterial carriage in smokers might be increased bacterial adherence to epithelial cells, which obscures the effect of MBL.

Cold temperature and low humidity are associated with increased occurrence of respiratory tract infections.

OBJECTIVE: The association between cold exposure and acute respiratory tract infections (RTIs) has remained unclear. The study examined whether the development of RTIs is potentiated by cold exposure and lowered humidity in a northern population. METHODS: A population study where diagnosed RTI episodes, outdoor temperature and humidity among conscripts (n=892) were analysed. RESULTS: Altogether 643 RTI episodes were diagnosed during the follow-up period. Five hundred and ninety-five episodes were upper (URTI) and 87 lower (LRTI) RTIs. The mean average daily temperature preceding any RTIs was -3.7+/-10.6; for URTI and LRTI they were -4.1+/-10.6 degrees C and -1.1+/-10.0 degrees C, respectively. Temperature was associated with common cold (p=0.017), pharyngitis (p=0.011) and LRTI (p=0.048). Absolute humidity was associated with URTI (p<0.001). A 1 degrees C decrease in temperature increased the estimated risk for URTI by 4.3% (p<0.0001), for common cold by 2.1% (p=0.004), for pharyngitis by 2.8% (p=0.019) and for LRTI by 2.1% (p=0.039). A decrease of 1g/m(-3) in absolute humidity increased the estimated risk for URTI by 10.0% (p<0.001) and for pharyngitis by 10.8% (p=0.023). The average outdoor temperature decreased during the preceding three days of the onset of any RTIs, URTI, LRTI or common cold. The temperature for the preceding 14 days also showed a linear decrease for any RTI, URTI or common cold. Absolute humidity decreased linearly during the preceding three days before the onset of common cold, and during the preceding 14 days for all RTIs, common cold and LRTI. CONCLUSIONS: Cold temperature and low humidity were associated with increased occurrence of RTIs, and a decrease in temperature and humidity preceded the onset of the infections.

Training improves physical fitness and decreases CRP also in asthmatic conscripts.

To study the respiratory and physical health of young men, 224 asthmatic and 668 non-asthmatic military conscripts were recruited from the intake groups of July 2004 and January 2005 in Kajaani, Finland. Factors affecting respiratory health were elicited by a questionnaire at the beginning of the service, and results of high sensitive C-reactive protein (hsCRP) determination, peak expiratory flow (PEF), and 12-minute running test were collected at the beginning and the end of the service. Respiratory infections were diagnosed by a study physician. Upon entering military service, asthmatics had frequent exercise- and cold-related asthma symptoms (69.6% and 76.3%), and 48% of them had no medication for asthma. At the beginning, 25.8% of asthmatics and 19.1% of non-asthmatics had a poor result of less than 2,200 m (p = 0.05) in the 12-minute running test, and after 180 to 362 days of service, the corresponding percentages were 11.7% and 9.7% (p = 0.434). The levels of hsCRP, a marker of low-grade systemic inflammation, decreased significantly among both asthmatics, 1.5 (p = 0.001), and non-asthmatics, 1.6 mg/L (p < 0.001). Asthmatic men had 0.2 and non-asthmatics 0.1 respiratory infections per month (p < 0.001). In summary, asthmatic conscripts can enhance their physical fitness by training similarly to non-asthmatic ones. Their levels of hsCRP also decrease.

The association between C-reactive protein levels and depression: Results from the northern Finland 1966 birth cohort study.

BACKGROUND: To investigate whether depressive episodes (previous, current single, and recurrent) are associated in both genders with highly sensitive C-reactive protein (hs-CRP) levels, earlier recommended for risk assessment of cardiovascular disease. The impact of the severity of current single and recurrent depressive episodes on this putative association was also investigated. METHODS: The genetically homogeneous Northern Finland 1966 Birth Cohort was followed until age 31, when, in a cross-sectional setting (n = 5269), the highly sensitive enzyme immunoassay (hs-EIA) method was used to measure CRP concentration. Depressive episodes were defined through mailed questionnaires, including Hopkins Symptom Checklist-25 (HSCL-25) and information on self-reported, doctor-diagnosed depression. RESULTS: After adjusting for confounders, logistic regression analyses showed that in male subjects, elevated hs-CRP levels (> or =1.0 mg/L) increased the probability for severe current and recurrent depressive episodes 1.7-fold and 3.1-fold, respectively. Correspondingly, an hs-CRP level of >3.0 mg/L increased the probability for recurrent depression up to 4.1-fold. In female subjects, no statistically significant associations were found. CONCLUSIONS: Our results support the hypothesis that an activation of systemic inflammatory processes may contribute to the pathophysiology of severe depression in men. Further investigations are needed regarding the impact of our findings on diagnostic/treatment strategies concerning severe and, especially recurrent, depression in men.

Inhibitory effect of heparan sulfate-like glycosaminoglycans on the infectivity of Chlamydia pneumoniae in HL cells varies between strains.

Glycosaminoglycans are known to participate in the attachment of several chlamydial strains. We studied the effect of heparin, enoxaparin, low-molecular-weight heparin, chondroitin sulfate A, and heparinase I on the infectivity of Chlamydia pneumoniae strain CWL029 and two Finnish isolates, Kajaani 7 and Parola, in an HL cell line which is epithelial in origin. Two Chlamydia trachomatis strains, L2 and E, were used for comparison. The infectivity of all C. pneumoniae strains and C. trachomatis serovar E was inhibited not only by heparin derivatives but also by chondroitin sulfate A and heparinase treatment. Treatment of host cells with heparin derivatives and heparinase was also inhibitory. Different chlamydial strains and species seem, however, to vary in their ability to use heparin in their attachment to host cells.