Endocrine Abnormalities and Cytokines

Several endocrine abnormalities, such as low levels of testosterone and growth hormone and increased production of cytokines, have been correlated with weight loss in AIDS, while adrenal and thyroid hormones show conflicting patterns [63]. The synergic action of TNF and other cytokines is considered the most probable mechanism causing cachexia [8,79,80] (Fig. 6,7).

The clinical symptoms of anorexia, nausea, fever, asthenia, fatigue, lethargy, myalgia, sickness, diarrhoea, anaemia, leucocytopaenia, tachycardia, headache, neurovegetative disturbances, etc., can be attributed to the release of cytokines by macrophages and activated inflammatory cells.

Lipid metabolism disturbances, anorexia, and weight loss together lead to cachexia and are caused by the combined action of TNF, IL-1, IL-6, and IFN-y, the production of each being stimulated by infections and cancer [82, 83]. We demonstrated [84] high levels of TNF-a in HIV patients who had lost more than 10% of their ideal weight (Table 3).

Intracellular

Intracellular

Fig. 6. Pattern of cytokine production. LPS, lipopolysaccharide; G-CSF granulocyte colony-stimulating factor; GM-CSF granulocyte/macrophage colony-stimulating factor. For other abbreviations, see text

Fig. 7. Regulation of tumour necrosis factor (TNF) synthesis in macrophages

Table 3. TNF blood levels in 50 AIDS patients

> 400 pg/ml

400-201 pg/ml

200-100 pg/ml

< 100 pg/ml

Disease

Disease

Disease

Disease

(n = 13)

(n = 14)

(n = 6)

(n = 17)

Toxo (2)

Toxo (1)

Crypto (1)

Toxo (3)

PCP (6)

PCP (4)

Lymphoma (1)

PCP (3)

HIV (2)

Toxo + KS (1)

TBC (1)

Salm (1)

MAC (2)

PCP + HSV (1)

CMV (1)

TBC (1)

PCP + Toxo (1)

MAC (2)

HIV (2)

Crypto (2)

Toxo + MAC(2)

Candida (1)

HIV (2)

VZV (1)

Toxo + PCP(1)

HIV (5)

Toxo, neurotoxoplasmosis; PCP, Pneumocystis carinii pneumonia; MAC, Mycobacterium avium complex; HSV, herpes simplex virus; KS, Kaposi's sarcoma; Crypto, cryptosporidiosis; TBC, tuberculosis; CMV, cytomegalovirus; Salm, salmonellosis; VZV, varicella zoster virus

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