Ullum, Henrik*; Diamant, Marcus†; Victor, Jette*; Gøtzsche, Peter C.*; Bendtzen, Klaus†; Skinhøj, Peter*; Pedersen, Bente Klarlund*
To the Editor: Increased levels of circulating interleukin-6 (IL-6) and soluble IL-6 receptors (sIL-6R) have been described in HIV-seropositive patients (1). Furthermore, increased levels of IL-6 have been related to the development of hypergammaglobulinemia or the presence of Kaposi's sarcoma or lymphomas in HIV-infected patients, and IL-6 has been reported to increase replication of HIV (1). We measured plasma IL-6 by a double-sandwich enzyme-linked immunosorbent assay (ELISA) (2) in 341 HIV-seropositive patients (308 were men; the median age was 39 years; quartiles were 33-47 years) and 81 age- and sex-matched healthy controls not at risk for HIV infection. The seropositive patients consisted of 263 homosexual or bisexual males, 52 reportedly heterosexually transmitted persons, nine drug addicts, five hemophiliacs, 10 persons infected by blood transfusions, and nine persons with unknown risk factors (seven patients had more than one risk factor). The number of patients with AIDS was 110; AIDS-defining events were Pneumocystis carinii pneumonia (PCP) in 55, candidiasis of the esophagus, trachea, bronchi, or lungs in 26, Kaposi's sarcoma in 26, toxoplasmosis of the brain in 19, cytomegalovirus infection in 11, HIV wasting syndrome in eight, disseminated atypical mycobacteriosis in six, lymphomas in five, and other AIDS-defining diseases in 18 patients. sIL-6R was measured by ELISA (3) in the plasma of 46 seropositive patients (13 with AIDS) and 14 healthy controls. IgA, IgG, and IgM were measured in the serum of 316 patients by immunochemical assay (Behringwerke AG, Marburg, Germany).
Both the patients with AIDS and those without AIDS had increased plasma levels of IL-6 compared with controls whereas patients with AIDS and patients without AIDS had similar plasma IL-6 levels (Table 1). Levels of sIL-6R in plasma did not differ between groups (Table 1). Levels of IgG and IgA were elevated in both patients with AIDS and those without AIDS, whereas IgM levels for both groups of patients were within the normal range of the laboratory (Table 1). Patients with AIDS had higher levels of IgA but lower levels of IgG and IgM compared with patients without AIDS (Table 1). Plasma levels of IL-6 and sIL-6R did not correlate with serum levels of IgA, IgG, and IgM in patients (r = -0.02, p = 0.8; r = 0.05, p = 0.4; r = -0.02, p = 0.7 for IL-6; and r = 0.02, p = 0.9; r = 0.1, p = 0.5; r = 0.1, p = 0.5 for sIL-6R, respectively), and the 43 patients with elevated IL-6 had unchanged levels of immunoglobulins compared with those with normal IL-6 levels (data not shown). Plasma levels of IL-6 did not correlate with the CD4 counts in patients or controls (r = 0.03, p = 0.6 and r = -0.04, p = 0.7, respectively), whereas plasma levels of sIL-6R did correlate with the CD4 counts in patients (r = 0.3, p = 0.3) but not in controls (r = 0.04, p = 0.9). AIDS patients with Kaposi's sarcoma and AIDS patients with lymphomas had unchanged levels of IL-6 compared with other AIDS patients (data not shown), and patients with elevated plasma IL-6 had unchanged levels of sIL-6R (139, 129-182 ng/ml; median and quartiles). These results confirm previous reports of increased circulating levels of IL-6 in patients with HIV infection, whereas levels of IL-6 are not further increased with the development of AIDS or with losses of CD4+ cells. In contrast to the finding of increased levels of IL-6, we could not confirm a previous finding of increased circulating sIL-6R in HIV-infected patients, and the data do not support a role of increased circulating levels of IL-6 for the development of hypergammaglobulinemia or malignant diseases in HIV-infected patients. Because IL-6 can induce an increased replication of HIV, however, increased levels of IL-6 could be an important pathogenetic factor in AIDS development. Thus, the clinical significance of IL-6 and other immunological parameters (4) will be studied prospectively in this group of HIV-seropositive patients.
Acknowledgment: The study was supported by the AIDS foundation (Copenhagen), Danish Medical Research Council 9400942 and 9502920, The Danish National Research Foundation 504-14, State University Hospital (Rigshospitalet), and The Danish Biotechnology Program.
*Henrik Ullum; †Marcus Diamant; *Jette Victor; *Peter C. Gøtzsche; †Klaus Bendtzen; *Peter Skinhøj; *Bente Klarlund Pedersen
*Department of Infectious Diseases; †Institute for Inflammation Research; Rhimia Centre; Rigshospitalet; Copenhagen, Denmark
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