The Effects of Peg-Interleukin-2 and Interleukin-2 on Essential Hypertension and Cellular Immune Function in the Spontaneously Hypertensive Rat

Abstract

The effects of recombinant human interleukin-2 covalently linked to polyethylene glycol (PEG-IL-2) or interleukin-2 (IL-2) on hypertension and in vitro suppressor T cell function in the spontaneously hypertensive rats (SHR) were investigated. Male young prehypertensive(4 weeks old) SHRs and adult (10 weeks old) SHRs with established hypertension were injected with low (5,000 units (u)/kg) or high (50,000-100,000 u/kg) dose of PEG-IL-2 or IL-2 as a single bolus or repeated injections. Systolic blood pressure was measured twice weekly using the tail-cuff technique. Systolic blood pressure in the PEG-IL-2 or IL-2 treated animals, irrespective of age, dose, or route of injection, did not differ significantly from that measured in vehicle-treated controls over a 10 week period. Mean arterial pressure measured by intra-arterial catheter was 159 ± 7 mm Hg 10 weeks after treatment with repeated injections of 5,000 u/kg of PEG-IL-2 and 158 ± 9 mm Hg in vehicle-treated controls. All rats injected with IL-2 had IL-2-specific IgG antibody in their sera. None of the PEG-IL-2 treated rats had any detectable anti-IL-2 antibodies in their sera. Thus, PEG-IL2 showed far less immunogenici than IL-2. Suppressor T (Ts) cells generated from adult SHR spleen cells failed to supress pokeweed mitogen (PWM)-driven immunoglobulin G (IgG) synthesis. PEG-2 or IL-2 supplementation both in vitra and in vivo restored the ability of adult SHR to enerate Ts cells able to inhibit IgG synthesis. Our data suggest that PEG-IL-2 or IL-2 administration does correct a rominent defective Ts cell activity found in adult SHR, but that correction or this immune abnormality is not attended by an attenuation of hypertension.

Key Words:

• Interleukin-2
• Hypertension
• Cellular immunity