Hypoxia and inflammatory synovitis: observations and speculation.

Abstract

In recent years considerable research interest has been directed at studying the biological consequences of tissue hypoxia. As this work progresses it becomes increasingly apparent that tissue hypoxia has complex biological consequences. Much is now known about the natural defences of the body to hypoxia, including heat shock protein synthesis and angiogenesis. These systems are normally under rigid control, but this would seem not so in the rheumatoid joint. This accumulation of knowledge has prompted the belated reawakening of interest in joint hypoxia; it is now clear that an understanding of the physiological and pathological effects of joint hypoxia is of great importance to both clinical and research rheumatology.This review outlines joint hypoxia from a historical perspective and offers explanations for the phenomenon. Some of the more pertinent implications of hypoxia in the context of inflammatory synovitis are discussed.

Bacterial delivery of a novel cytolysin to hypoxic areas of solid tumors

“…Importantly, FF+20* driven lacZ expression in normoxic conditions was negligible ( Figure 1a). Moreover, we showed that the FF+20* promoter retained 84 and 77% activity in severe hypoxic conditions (0.1 and 0.5% O 2 , respectively; Figure 1b), which is equivalent to pathological levels of hypoxia in vivo [15][16][17][18] and importantly, that FF+20* driven lacZ expression returned to a minimal level (4% activity) in mild hypoxic or normoxic conditions (X5% O 2 ; Figure 1b). Thus we have designed a promoter, FF+20*, with the characteristics necessary to restrict transgene expression to severely hypoxic tissues and ensure negligible expression in extra-tumoral (that is, normoxic) tissues.…”

Inflammatory Cytokines and Hypoxia Contribute to 18F-FDG Uptake by Cells Involved in Pannus Formation in Rheumatoid Arthritis

“…It has been shown that TNFa and IL-1 induce the cell cycle progression of fibroblasts (17,18). In fact, synovial fibroblasts in joints affected by RA showed increased proliferative activity and increased glycolysis compared with those in normal joints (19,20). Fibroblast proliferation may be one of the dominant causes of 18 F-FDG accumulation in vivo.…”

Intracellular alkalization causes pain sensation through activation of TRPA1 in mice

“…It is well documented that several pathological conditions (inflammation or sudden cessation of blood flow) cause pain sensation through tissue acidification (62) and that TRPV1 activation is involved in some of these responses (23,24). Tissues seem to be less frequently exposed to alkaline than acidic conditions.…”