Changes in the levels of some acute-phase proteins in human immunodeficiency virus-1 infected patients, following interleukin-2 treatment

Abstract

Intermittent interleukin (IL)-2 administration to human immunodeficiency virus (HIV)-1 infected patients is well documented and generally used, but there is limited information about the changes of acute-phase protein (APP) levels in response to this treatment. Fifteen patients undergoing highly active anti-retroviral therapy (HAART) treatment, with undetectable viral load, but low CD4+ cell count (<300/microl), have been treated with 3.6 M IU Proleukine administered twice daily by subcutaneous injection over 5 days. C-reactive protein (CRP), D-dimer, C3, C9, C1-inh and alpha-2HS glycoprotein levels were measured immediately before IL-2 administration, as well as on day 5 and 2-3 weeks thereafter. After IL-2 administration, both mean D-dimer and CRP levels increased significantly (P<0.001), but returned (P<0.001) to baseline within the subsequent 2-3 weeks. Alpha-2HS glycoprotein decreased immediately after IL-2 administration. No significant differences were detected in the levels of C3, C9 and C1-inh. A significant, positive correlation (r=0.5178, P=0.0008) was ascertained between the changes of CRP level, measured immediately before as well as 5 days after IL-2 administration, and changes in CD4 T cell counts measured 2-3 weeks before and after treatment, respectively. IL-2 administration induces rapid elevation of two major APPs (CRP, D-dimer). The positive correlation observed between the changes of CRP levels and CD4+ cell counts after IL-2 administration may indicate that the abrupt, but transitory overproduction of CRP might contribute to the CD4+ cell count-increasing effect of the drug and/ or may be associated with serious side effects.

Fig. 1

(a) Changes of absolute CD4⁺ T cell numbers 2–3 weeks before and after treatment. ***P < 0·001. (b) Changes of absolute CD4⁺ T cell numbers 2–3 weeks before (B) and after (A) treatment, in patients who received more interleukin-2 cycles.

Fig. 2

Changes of d-dimer levels following interleukin-2 treatment. d-dimer levels increased sharply from day 0 to day 5 and decreased after the discontinuation treatment. Presented values are means. ***P < 0·001.

Fig. 3

(a) Changes of C-reactive protein (CRP) level during interleukin-2 treatment of human immunodeficiency virus-infected patients (with the exception of patients co-infected by Pneumocystis and Cryptosporidium). Presented values are means. ***P < 0·001. (b) Changes of CRP concentration immediately before (B) and after (A) treatment, in patients who received at least three cycles.

Fig. 4

Changes in the levels of (a) C3, (b) C1-inh, (c) C9 and (d) alpha-2HS glycoprotein during follow-up. Presented values are means. *P < 0·05.

Fig. 5

Correlation between the differences in serum C-reactive protein levels and absolute CD4⁺ T cell numbers measured 2–3 weeks before and after interleukin-2 treatment.