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3.4 Pharmacological Activity
3.4.1 Antiinflammatory Activity
3.4.1.1 Cytokine and Chemical Substances Correlated with Inflammatory Activity
Chitosan is a linear polymer of N -acetyl-d-glucosamine and deacetylated glucosamine
that shares some characteristics of glucosaminoglycan and hyaluronic acid, suggesting
related bioactivities [142]. Chitosan enhances the functions of inflammatory cells such as
polymorphonuclear leukocytes, macrophages (MU), and fibroblasts [143-146]. TNF-α was an
inflammatory cytokine, which was produced by the various cells including macrophages,
lymphocytes, neutrophils, and mast cells. TNF-α is known to be a key mediator for the
induction of apoptosis and development of humoral immune response. However, at high
concentrations, TNF-α has disadvantageous effects, such as inducing tissue injury and
potentiating septic shock. TNF-α may have a homeostatic effect in limiting the extent of an
inflammatory response as well as acting as an antimalarial agent and being functional in
intramembranous bone repair.
Interleukin-6 (IL-6) is a multifunctional cytokine that plays important roles in host defense,
acute-phase reactions, immune responses, nerve cell functions, and hematopoiesis. It is
expressed by a variety of normal and transformed lymphoid and nonlymphoid cells. The
production of IL-6 is upregulated by numerous signals such as mitogenic or antigenic stimu-
lation, lipopolysaccharides (LPSs), calcium ionophores, cytokines, and viruses. Elevated
serum IL-6 levels have been observed in a number of pathological conditions, including
bacterial and viral infections, trauma, autoimmune diseases, and inflammations.
Nitric oxide (NO) is a highly reactive free radical involved in a number of physiological
and pathological processes. NO may play an important role in the pathophysiology of
numerous diseases. In numerous mammalian cells and tissues, the oxidation of the termi-
nal guanidino nitrogen of l-arginine (Arg), yielding NO and citrulline, is catalyzed by
different NO synthases. The role of NO is well established in the relaxation of vascular
smooth muscle, in the inhibition of mitogenesis and growth of glomerular mesangial cells,
and in macrophage toxicity. NO acts immunologically as a cytotoxic agent on invading
microorganisms in macrophages or on tumor cells.
LPS is one of the major constituents of the outer membrane of Gram-negative bacteria,
and LPS recognition and signal transmission are among the key events in the host defense
reaction toward Gram-negative bacteria. Humans are constantly exposed to low levels of
LPS through infection. Many different cell types such as neutrophils and macrophages
can respond to LPS by releasing potent inflammatory mediators such as IL-8 and TNF-α
to destroy invading bacteria. Additionally, epithelial and endothelial cells as well as
smooth muscle cells have also been shown to be targets for LPS stimulation, and activation