Abstrakt
Systemic inflammation involves powerful immune response that interferes with homeostatic regulation of many physiological processes including those controlling appetite and nutritional balance. In advanced chronic diseases, such as chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, chronic infection or sepsis, renal failure, heart failure and cancer, the immune response is frequently exaggerated insofar as it ultimately leads to a severe debilitating state known as cachexia.
It is well known that this condition deteriorates the quality of life and predicts increased morbidity and mortality. According to a recent definition, cachexia is characterized as a complex metabolic syndrome associated with a loss of body weight.
In this condition, inflammation, anorexia, insulin resistance and increased muscle protein breakdown are present and result in depletion of skeletal muscle with or without a loss of fat mass (Evans et al., 2008). These hallmarks considerably distinguish cachexia from other conditions that are also associated with catabolic/anabolic imbalance or body composition disorders (e.g. starvation, dehydratation, sarcopenia, malabsorption, hyperthyroidism and lipoatrophy).
At present, despite the clinical relevance of cachexia and an increasing interest of scientists and clinicians in this topic, its causal mechanisms are not yet completely understood. There is a large body of evidence that inflammation is a crucial factor in the pathogenesis of cachexia.
Since proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, and IL-6, are able to modulate brain functions, dysregulate hormone levels or cause metabolic disturbances, these molecules are of paramount importance. Nonetheless, in the multidimensional nature of cachexia it is apparent that this process is a very complex one and the underlying mechanisms do not encompass only the cytokines, but rather cytokines along with many other inflammatory mediators, hormones, neurotransmitters and metabolic factors.
This chapter reviews the current knowledge about the role of cytokines in the pathogenesis of anorexia, insulin resistance and muscle catabolism as the main features of cachexia in human inflammatory diseases and their experimental animal models. The presented insight into the intertwined immune, neuroendocrine and metabolic pathways contributing to cachexia may lead to a better understanding of this pathological phenomenon appearing in chronic diseases and to possible directions for future research.