Alterations in IgA and complement system of rats exposed to intense hypobaric hypoxia (7620m) at different time duration

Abstract

An altitude above 8000 feet is considered as high altitude which includes oxygen-compromised environment. Such environment results in a condition called hypobaric hypoxia (HH) which may induce diseases/problems in different organ systems. Diseases like Acute Mountain Sickness (AMS), High Altitude Pulmonary Edema (HAPE), and High Altitude Cerebral Edema (HACE) occur commonly in natives, mountaineers and soldiers recruited at high altitude. While much work has been done on the effects of high altitude but its impact on immune system is less studied so far. Immune system is a network of different cells, tissues and organs which help in defending the body from foreign substances and other harmful stressors. It gets affected by extreme environments, invading harmful micro-organisms and disease conditions. It is now established that stressful conditions do affect the immune system. In some reports, high altitude environment has shown to affect different immune cells like T-cells, B-cells, NK cells and macrophages.1,2 Studies on harsh environment of Antarctica also suggested that stressful conditions of Antarctica lead to increased serum IgA levels.3 One of the important branches of immune system is the Complement system which helps the immune cells to get activated against the invading micro-organisms and different inflammatory molecules, thus provides a bridge between innate and adaptive immune response.4 Complement system is activated via three pathways namely classical, alternate and lectin.5 In many studies, Complement system has also been shown to get activated by different stressful environments. In a study, performed on human subjects who went to Antarctica, it has been shown that stressful conditions led to the activation of complement cascade. Factors like C3, C4, C3a, C4a, C5a and Complement Factor B were modulated in the summer as well as winter over expedition members.6 A Study on rats sensitive to hypoxia revealed activation of complement system components with different degrees of hypoxia exposure for maximum of 3 days.7 Also, levels of complement protein like C4 has been seen to alter on acute HH exposure8 HH is a stressful condition; human go to pilgrimages, mountains or works at such high altitude which results in immune compromisation. IgA has been seen to play a major role in defending to infections on mucous membranes. It has been seen that there is a higher incidence of infections in people going to high altitudes, therefore the study was done in an attempt to understand immunity of people at high altitude, changes in IgA levels and complement factors were studied. As in rats, pathological changes are majorly seen at an altitude of 25,000 ft,9 the rats were exposed to simulated hypobaric hypoxic conditions in specially designed decompression chamber. Our study revealed that HH significantly modulated the levels of IgA and complement factors in rats. The results can be applied to unfold mechanism of immune system activation in humans during high altitude (hypobaric hypoxia) stay.