Chapter 1. Introduction

Chlamydia pneumoniae is a common obligate intracellular bacterium that causes upper and lower respiratory infections worldwide (Grayston et al. 1990). In addition to acute infections, several chronic inflammatory diseases have been presumptively associated with C. pneumoniae infection. Increasing evidence implicates that a persistent lung infection caused by C. pneumoniae may contribute to the initiation, exacerbation and promotion of asthma symptoms (reviewed by Hahn 1999). A causal association between C. pneumoniae infection and asthma is biologically plausible based on the observations that asthma is a chronic inflammatory disease of the airways, and that chlamydiae are known to produce chronic inflammatory damage in target organs. Whether C. pneumoniae lung infections activate the same immunopathologic mechanisms that have been demonstrated for other chlamydial diseases has not been explored systematically.

C. pneumoniae infection has also been linked with atherosclerosis — another chronic inflammatory disease. Evidence of a serological association of C. pneumoniae with atherosclerosis and its complications was first presented by Saikku et al. (1988a). Since then, a large number of seroepidemiological studies have confirmed these findings (reviewed by Leinonen & Saikku 2002). The actual presence of C. pneumoniae in atherosclerotic lesions has also been demonstrated in a number of studies and by various methods (reviewed by Kuo & Campbell 2000, Taylor-Robinson & Thomas 2000). Moreover, the presence of C. pneumoniae-specific T lymphocytes in atherosclerotic tissue specimens suggests that C. pneumoniae participates in the maintenance of the inflammatory response in the tissue and may thus be involved in the progression of the disease (Halme et al. 1999, Curry et al. 2000, Mosorin et al. 2000). In experimental animals, C. pneumoniae infection has been found to induce inflammatory changes and calcified lesions containing Chlamydia (Fong et al. 1997, Laitinen et al. 1997) and to accelerate the development of atherosclerosis (Moazed et al. 1999).

Both asthma and atherosclerosis are chronic inflammatory diseases. C-reactive protein (CRP) is a typical acute phase reactant, whose concentration increases within hours of any tissue-damaging, inflammatory event, including acute bacterial infection (Ablij & Meinders 2002). Slightly elevated CRP levels, measured by high-sensitivity assays, have been shown to predict cardiovascular events (Rifai & Ridker 2001, Ridker et al. 2002). The role of CRP in asthma has not been investigated.

Heat shock proteins (Hsp) are a class of evolutionarily highly conserved proteins, which are produced by all organisms in response to stress or injury, including infection, to protect cells from unfavourable conditions (Kaufmann 1990). It has been suggested that Hsp60 may play a role in the pathogenesis of chlamydial infections. It is overproduced in persistent infections (Beatty et al. 1994a), and it has been associated with the hypersensitivity and immunopathology seen in these infections (Morrison et al. 1989b). There is increasing evidence on the association between antibodies to chlamydial Hsp60 and the development of immunopathological damage following C. trachomatis infections (Peeling & Mabey 1999), but the role of Hsp60 in C. pneumoniae infections has not been clarified yet. Due to the high sequence homology between bacterial and human Hsps, these proteins have been postulated to be critical antigens in autoimmune diseases. There are studies suggesting that the host immune response to microbial Hsp60 may lead to autoimmunity to human Hsp60 and, consequently, to the development of atherosclerosis (Kol et al. 1998, Mosorin et al. 2000,Wick et al. 2001).