Chlamydia pneumoniae and the Cytokine Response
Infection with Chlamydia pneumoniae has been shown to cause host cells to produce, for example, elevated levels of the following cytokines:
Given this, it is important then to understand a little bit about cytokines and their functions and effects on the body in order to understand the potential effects that a persistent C. pneumoniae infection may have on the body.
In a nutshell, cytokines are really just chemical messengers that among other functions, are used by our immune systems to coordinate the activities of the various immune cells as well as the various organs of the body that are important for an effective immune response. Cytokines play an important role in stimulating the immune response, properly targeting the immune response, and, importantly, limiting the immune response.
Very simply put, cytokines can be classified by function as being:
- autocrine, if the cytokine acts on the cell that secretes it
- paracrine, if the action is restricted to the immediate vicinity of a cytokine's secretion
- endocrine, if the cytokine diffuses to distant regions of the body (carried by blood or plasma) to affect different tissues
Cytokines work together through extremely complex interactions in what has been termed the Cytokine Network (or Cytokine Cascade) through:
- pleiotropy, if the cytokine has different biological effects on different target cells
- redundancy, if two or more cytokines may have the same effect on a target cell
- synergy, if the effect of more than one cytokine produces an effect greater than the additive effect of each cytokine alone
- antagony, if a cytokine or cytokines decrease the effects of another cytokine or they decrease the effects of each other
As mentioned above, cytokines play an important role in inflammation, and cytokines can loosely be divided into two categories based on their effects on inflammation:
- pro-inflammatory cytokines, those cytokines that favor or accelerate inflammation
- anti-inflammatory cytokines, those cytokines that dampen or counteract inflammation
Really it is the balance between these two categories of cytokines that is important in determining the net effect of the inflammatory response; however, the cytokines that have been shown to be elevated in C. pneumoniae infection are generally regarded as pro-inflammatory, with IL-1, IL-6, TNF-a being considered the major pro-inflammatory cytokines.
Cytokines, through their endocrine functions, have also been shown to play an important role in the Neuroimmune Network, and they have been shown to be responsible for communication between the immune system and neuroendocrine organs (including the brain, pituitary, thyroid, parathyroid, pancreas, adrenal glands, testes, ovary, etc). Neural targets that control thermogenesis, behavior, sleep, and mood can be affected by pro-inflammatory cytokines.
Indeed, elevated IL-1, IL-6 and TNF-a appear to be widely known to have neuroendocrine effects (see diagram), while elevated levels of many of these cytokines have been associated with various psychiatric or "mential" disorders in studies, potentially suggesting a reason for why infection with C. pneumoniae has been associated with anxiety and depression:
And increased levels of TNF-a have also been implicated in insulin resistance:Secretion of tumor necrosis factor-alpha shows a strong relationship to insulin-stimulated glucose transport in human adipose tissue
There are, of course, many other examples of ways these cytokines likely influence neuroendocrine functions. Those listed above are really just a small subset, listed to explain the potential implications of elevated levels of these cytokines.
An uncontrolled feedback loop between cytokines and the various immune cells can cause what has been termed a Cytokine Storm or Systemic Inflammatory Response Syndrome, which is basically an uncontrolled and exaggerated immune response to infectious or non-infectious assault. The following article discusses, in simple terms, a cytokine storm or overly aggressive immune response to pathogen (flu viruses in this case), but the same basic response occurs in a more limited way in any inflammatory reaction, including the inflammation that occurs with any infection, including the inflammation associated with C. pneumoniae:
In summary, in order to understand the full implications of infection by C. pneumoniae, it is important to understand the role that the associated elevated pro-inflammatory cytokines play in response to this pathogen, and it is important to understand that these elevated cytokines can effect the neuroendocrine network, potentially causing what might seem to be unrelated effects, including various thermogenic, behavioral, sleep, and mood effects in addition to the localized (or systemic) inflammation more generally recognized to be associated with this pathogen.