SUSCEPTIBILITY TO RESPIRATORY TRACT INFECTIONS IN YOUNG MEN: THE ROLE OF INFLAMMATION, MANNOSE-BINDING LECTIN, INTERLEUKIN-6 AND THEIR GENETIC POLYMORPHISMS, ACTA UNIVERSITATIS OULUENSIS D Medica 1069
|Kustantaja:||Oulun yliopisto|| |
|Oppiaine:||Lääketiede, farmasia|| |
|Sijainti:||Print Tietotalo|| |
|Tekijät:||RANTALA AINO|| |
Respiratory tract infections are the most common acute illnesses, and innate immunity andinflammation are important in defence against these infections. Mannose-binding lectin (MBL)mediates innate immune defences by recognising microbial structures. MBL deficiency caused bypolymorphisms in the MBL2 gene has been associated with susceptibility to recurrent infections.Interleukin-6 (IL-6) is a mediator of inflammatory response. Polymorphisms in the IL-6 and IL-6receptor (IL-6R) genes have been previously associated mainly with metabolic disorders andcardiovascular diseases. Chlamydia pneumoniae is a common pathogen in acute respiratory tractinfections, but it also has a tendency to cause persistent infections, which have been associated withcardiovascular diseases and its risk factors, such as obesity.
The aims of this study were to investigate if selected polymorphisms of the MBL2, IL-6 and IL-6R genes are associated with respiratory tract infections and markers of C. pneumoniae infection,and to study if persistent C. pneumoniae infection is connected with an elevated body mass index(BMI) in 893 Finnish male military conscripts. Respiratory tract infections were followed duringtheir military service and serum samples were collected at the beginning and end of their service andduring each infectious episode.
A variation in serum MBL levels between different MBL2 genotypes and a MBL deficiency inhomozygous exon 1 variant genotypes (at codons 52, 54 and 57) were observed. Low MBL levelsand MBL2 polymorphisms in exon 1 and promoter region were found to be risk factors forsusceptibility to respiratory tract infections as well as for positivity and a rise in C. pneumoniaeantibodies during military service.
Associations between IL-6R gene polymorphisms in the promoter region (-183G/A) and in intron1 and respiratory tract infections were found. In addition, the IL-6 -174G/C polymorphism wasassociated with persistently elevated C. pneumoniae antibodies and with slightly elevated serum C-reactive protein (CRP) levels, pointing to chronic C. pneumoniae infection.
Furthermore, persistent C. pneumoniae antibodies as a suggestive marker of chronic infection,and elevated serum CRP levels as a marker of systemic inflammation, were associated with anelevated BMI.
In conclusion, the findings support the role for MBL in susceptibility to infections and providenew information about the association between MBL and common respiratory tract infections. Theresults also suggest that the 5’ area of the IL-6R gene may be a possible candidate region forrespiratory tract infection susceptibility, and that IL-6 genetics may be associated with C.pneumoniae infection. The study also provides new information about the role of possible chronicC. pneumoniae infection in obesity.