Alveolar immune mediators in HIV-related pneumonia. Different role of IL-2 and IL-1 in inducing lung damage.
In order to elucidate the role played by alveolar cytokines in the pathogenesis of HIV-related lung damage, levels of interleukin (IL) 1 beta, IL-2, IL-6, tumor necrosis factor (TNF)-alpha, and interferon (Ifn) were assessed on supernatant of bronchoalveolar lavage fluid from 30 consecutive HIV-1 seropositive (HIVAb+) patients with clinical and radiologic evidence of pneumonia, from 20 HIV- seronegative (HIVAb-) patients with pulmonary sarcoidosis, and from 10 HIVAb- healthy control subjects. Cytokine levels were expressed as picogram (IL-1, TNF), nanogram (IL-6), and international unit (IL-2, Ifn) per milligram of albumin per deciliter. Total and differential cell counts, cytofluorimetric enumeration of CD3+, CD3+/DR+, CD4+, CD8+, and CD8+/CD16+ cells, as well as microbiologic investigations for opportunistic agents were performed on lavage pellets. HIV-related pneumonia was characterized by higher mean alveolar level of IL-2 (12 +/- 5 IU), and by more elevated mean counts of T cells (109 +/- 16), activated T cells (60 +/- 12), and CD8+ cells (90 +/- 13)/microliters if compared with both active sarcoidosis and control subjects, where respective values of 0.2 +/- 0.1 and 0.3 +/- 0.2 IU IL-2/mgAlb/dl, of 52 +/- 11 and 7 +/- 2 T cells, of 20 +/- 5 and 1.2 +/- 0.3 activated T cells, and of 11 +/- 2 and 3 +/- 0.6 CD8+ cells per microliter were found. HIV-infected patients with opportunistic lung infections (OIs) showed the highest mean IL-2 level (21 +/- 4 IU), and higher counts of both CD8+ (117 +/- 20) and CD8+/CD16+ (36 +/- 7) cells per microliter if compared with patients without evidence of OIs (respectively, 62 +/- 13 CD8+ and 18 +/- 3 CD8+/CD16+ cells per microliter). By contrast, extremely high IL-1 levels (1,463 +/- 760 pg), and IL-2 levels similar to control subjects (3.4 +/- 1.2 IU), were found in the absence of OIs. Different mechanisms depending respectively on IL-2-mediated cytotoxic cell recruitment and activation, or IL-1-mediated tissue injury may account for HIV-related lung damage, depending on the presence or absence of opportunistic agents.
Biglino
A
A
Istituto di Malattie Infettive, University of Torino, Italy.
Forno
B
B
Pollono
A M
AM
Ghio
P
P
Albera
C
C
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000378:metabolism; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000378:metabolism*; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D007372:Interferons / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D016131:Lymphocyte Subsets; D008297:Male; D011014:Pneumonia / Q000150:complications / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012507:Sarcoidosis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D007375:Interleukin-1; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons