The effects of PEG-interleukin-2 and interleukin-2 on essential hypertension and cellular immune function in the spontaneously hypertensive rat.
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-IL-2 showed far less immunogenicity than IL-2. Suppressor T (Ts) cells generated from adult SHR spleen cells failed to suppress pokeweed mitogen (PWM)-driven immunoglobulin G (IgG) synthesis. PEG-IL-2 or IL-2 supplementation both in vitro and in vivo restored the ability of adult SHR to generate Ts cells able to inhibit IgG synthesis. Our data suggest that PEG-IL-2 or IL-2 administration does correct a prominent defective Ts cell activity found in adult SHR, but that correction of this immune abnormality is not attended by an attenuation of hypertension.
Ofosu-Appiah
W
W
Department of Immunology, Masonic Medical Research Laboratory, Utica, NY 13501.
Ruggiero
C
C
Dzielak
D J
DJ
Antzelevitch
C
C
D000367:Age Factors; D000818:Animals; D000918:Antibody Specificity; D001794:Blood Pressure / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006973:Hypertension / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D011092:Polyethylene Glycols; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D007074:Immunoglobulin G; D007376:Interleukin-2; C067245:interleukin-2, polyethylene glycol-modified; D011092:Polyethylene Glycols