Infectious disease immunosuppression

While profound immunosuppression can lead to an increased incidence of infectious or neoplastic diseases, interpreting data from experimental immunotoxicology studies or epidemiological studies for quantitative risk assessment purposes can be problematic. This is because inadvertent exposures to immunotoxic agents may often be expressed as a mild-to-moderate change, reflected, for example, by a 15 to 25% decrement in an immune parameter compared to control values. To help address the clinical consequences of mild-to-moderate immunosuppression, we examined available experimental, clinical and epidemiological studies that examined the association between suppression of immune function and infectious disease, independent of the etiology of suppression. 

Considerable data is available suggesting thatmild-to-moderate immunosuppression can lead to an increase in infectious disease. The types of infections that occur tend to result from either common pathogens (e.g., causing upper respiratory tract infections) or latent viruses (e.g., herpes cold sores), rather than opportunistic organisms such as Pnuemocyctis carinii. These are usually not life-threatening, except in certain susceptible populations, such as the elderly. Opportunistic infections, in contrast, are more prevalent in individuals where severe forms of immunosuppression are present, such as primary immunodeficiency diseases or HIV/AIDS. 

Infectious disease studies are normally conducted over a short time, providing only snapshots and do not provide information on the consequence of chronic immunosuppression. The adverse health effects of chronic, low level immunosuppression have been addressed to some extent in transplant patients, primarily kidney transplants, who demonstrate an increase frequency of certain immunogenic tumors. 

Suppression of local (at the site of UV exposure) and systemic (at a distant, unexposed site) immune responses to a variety of antigens has been demonstrated in both humans and animals exposed to UV-B. There is reasonably good evidence that such immunosuppression plays a role in human carcinogenesis however, the implications of such immunosuppression for human infectious diseases are still unknown. 

Efficacious mAbs are used in a variety of therapeutic indications such as cancer, rheumatoid arthritis, Crohn s disease, psoriasis, organ transplantation, asthma, infectious diseases, and cardiovascular diseases, while for other diseases research and development is currently ongoing. The current three major therapeutic areas include oncology (eight mAbs against solid tumors and lymphoma/leukemia), inflammatory diseases (five mAbs), and the immunosuppression/prophylaxis or treatment of organ rejection in transplantation (three mAbs). The reader is referred to Chapter 12 for a detailed discussion on the exposure-response relationships and pharmacodynamics of therapeutically administered mAbs. 

Hypothermia is known to cause cardiac dysfunction, particularly arrhythmias (36,37). Careful temperature control and optimal antiar-rhythmic therapy can minimize this problem. However, to avoid severe circulatory dysfunction, knowledge of arrhythmias is required. Hypothermia may be associated with a suppression of the immunological system, which exposes patients to the danger of severe infections. Schwab et al. reported that 7 of 25 stroke patients undergoing hypoth-ermiatherapy suffered a septic syndrome (17). In our hypothermic study, none of the 13 patients who underwent hypothermia therapy for 3-7 d developed severe infectious diseases. However, the remaining patient, who underwent 10 d of hypothermia because of massive cerebral edema, developed septic shock on the 10th day of hypothermia treatment. The immunosuppressive effect appears to be correlated with the depth and... 

Natural products, in particular those produced by microorganisms, have proved to be a rich source of useful signal transduction inhibitors with a variety of mechanisms of action. They continue to be of great interest as a source of new signal transduction inhibitors with potential for therapeutic use in the areas of immunosuppression, oncology and infectious disease. 

The immunosuppressive properties of Lei gong teng can promote the development of infectious diseases (42). 

In immunosuppression, one or more parts of the immune system are impacted. This results in impaired immune system function and reduced resistance to foreign chemical and biological agents that attack the body and can lead to increased incidence of infectious disease and cancer. 

Laboratory assessment includes indicators of general operative health (e.g., electrolytes, acid-base status, clotting profile, full blood cell count, and cross-matching). In addition, full human leukocyte antigen (HLA) tissue typing is undertaken, in addition to a full screen for infectious diseases, particularly cytomegalovirus (CMV), hepatitis, herpes, and HIV status, as these infections can be activated by immunosuppressive therapy. 

Immunology/infectious diseases Diseases affecting the defense mechanisms of the body. Studies in this area include AIDS, auto-immune diseases, bacterial infections, chronic fatigue syndrome, common cold, genital herpes, genital warts, hepatitis, HIV infections, immunosuppressive, influenza, lyme disease, meningitis, parasite and protozoan infections, strep throat, vaccines, viral infections, and others. 

Infectious Diseases. Resistance to a variety of organisms, including BCG, cryptococcus, and Candida, has been shown to be increased in immunosuppressed animals following in vivo treatment with TF5 (Collins and Auclair, 1979 Collins and Morrison, 1979 Bistoni et al., 1982 Ishitsuka et al, 1983). The basis for this increased resistance may be explained by studies showing that mouse strains with low resistance to Candida or BCG have increased resistance and elevated production of two lymphokines, MIF and 7 interferon following in vivo treatment with TF5 (Neta and Salvin, 1983 Salvin and Neta, 1983). Similar results were seen with Taj. In another model, interferon production in response to Newcastle s disease virus infection was also increased by in vivo treatment with TF5 or Ta (Huang et al., 1982). 

Total Artificial Heart. Although heart transplants have been performed since the pioneering work of Christian Barnard in 1967, this procedure always requires a donor heart, which may not always be available. In addition, the body does tend to reject any implanted organs as undesired foreign material, and close matching of the tissues is difficult at the best. Although various immunosuppressant drugs can minimize this problem, the patient becomes more susceptible to infectious disease. A total artificial heart (TAH) would offer at least a partial answer to both of these problems. 

Immunosuppression clearly influences health in old age, but at a potentially serious cost. Even so, there are grounds for hope, particularly if we gain the upper hand in the battle against infectious disease we know that it is possible to lower the probability of age-related diseases by modulating the immune system. Whether or not this is a practical goal depends on exactly how it is done. 

The immune system plays a major role in protecting the host from infectious disease and, arguably, from cancer. This is demonstrated by the association between the therapeutic use of chemical immunosuppressants (i.e., in cancer chemotherapy or organ transplantation) and an increased incidence of infections (1) and certain cancers (2). This relationship is also illustrated by the Acquired Immune Deficiency Syndrome (AIDS), in which a loss of immune responsiveness is associated with infection with Pneumocysti s carinii and other... 

---