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3. BACTERIA CAN INDUCE AND SUSTAIN CHRONIC INFLMMATION AND AMYLOIDOSIS

Bacteria are powerful inflammatory stimulators. It has been known from almost a century that chronic bacterial infections (e.g. rheumatoid arthritis, leprosy, tuberculosis, osteomyelitis) are frequently associated with amyloid deposition. Experimental amyloidosis can be induced by injecting living, attenuated or killed bacteria, LPS or bacterial peptidoglycan to experimental animals (Picken, 2000).

In bacteria, the cell wall consists of peptidoglycan, a complex polysaccharide composed of two sugar derivatives, N-acetylglucosamine and N-acetylmuramic acid and a small group of amino acids. Peptidoglycan is found in the wall of virtually all Eubacteria. It is absent in the evolutionary higher plant and animal cells (Eukaryotes). Bacterial cell walls are highly resistant to degradation by mammalian enzymes and thus may provide a persisting inflammatory stimulus (Ohanian and Schwab 1967; Lehman et al., 1983; Fox, 1990). It has been shown that human intestinal bowel contains soluble bacterial cell wall components that are arthropathic in an animal model [Stimpson et al., 1986; Fleming et al., 1986]. The bacterial peptidoglycan, the surface molecule lipopolysaccharide (LPS) and bacterial lipoproteins are powerful inflammatory and amyloidogenic factors.  Poorly degradable "bacterial remnants" or alternatively, "dormant" fastidious bacteria may persist indefinitely in the affected organs acting as a chronic antigenic stimulus inducing and sustaining chronic inflammation [Fox, 1990]. Bacteria or their synthetic or natural components such as bacterial peptidoglycan and LPS have a variety of biological actions in mammals. They are inflammatory cytokine inducers, activate the complement pathway, affect vascular permeability, generate nitric oxide, induce apoptosis and are amyloidogenic (Fox, 1990). All these processes are involved in the pathogenesis of AD. Already in 1907, Fischer suggested that senile plaques may correspond to colonies of microorganisms.