Interleukin-2 induces early multisystem organ edema mediated by neutrophils.
Interleukin-2 (IL-2), an agent known to activate neutrophils (PMN) with thromboxane (Tx)B2 release, produces pulmonary edema within 6 hours of intravenous infusion. This study tests the role of PMN in mediating the edema. Anesthetized rats received 10(6)U recombinant human IL-2 (n = 15) or vehicle (n = 14) as a constant intravenous infusion during a period of 1 hour. At this time there was leukopenia 3.63 +/- 0.43 (x10(3)/mm3) relative to vehicle-infused control rats 6.12 +/- 0.86 and a decline in PMN, 2.19 +/- 0.14 relative to control value of 3.33 +/- 0.05 (both p less than 0.05). After 6 hours edema, as measured by increase in the wet to dry weight (W/d) ratio, was present in the lungs (4.93 +/- 0.20 relative to control 4.06 +/- 0.10), heart (4.09 +/- 0.11 versus 3.76 +/- 0.08), liver (3.50 +/- 0.10 versus 3.18 +/- 0.10), and kidney (4.25 +/- 0.07 versus 4.00 +/- 0.07) (all p less than 0.05). There was increased lung permeability demonstrated by bronchoalveolar lavage fluid protein concentration of 1970 +/- 210 micrograms/mL relative to control 460 +/- 90 micrograms/mL (p less than 0.05). Interleukin-2 resulted in lung PMN sequestration of 53 +/- 7 PMN/10 high-power fields (HPF) relative to 23 +/- 2 PMN/10 HPF in controls (p less than 0.05) and increased plasma TxB2 levels to 1290 +/- 245 pg/mL relative to control 481 +/- 93 pg/mL (p less than 0.05). Pretreatment of other rats (n = 8) with selective anti-rat neutrophil antiserum 18 hours before the experiment led to a peripheral PMN count 10% of baseline and prevented edema in the lungs (W/d ratio 4.20 +/- 0.16) and heart (3.67 +/- 0.07) (both p less than 0.05) but not liver or kidney. Protein in lung lavage was reduced to 760 +/- 220 micrograms/mL (p less than 0.05). The protection afforded by leukopenia was associated with lack of PMN sequestration and prevention of the increase in plasma Tx levels (484 +/- 120 pg/mL, p less than 0.05). These data indicate that the rapid induction of lung and heart edema with a 1-hour infusion of IL-2 in the rat is mediated, in large part, by activated PMNs.
Welbourn
R
R
Department of Surgery, Harvard Medical School, Boston, Massachusetts.
Goldman
G
G
Kobzik
L
L
Paterson
I
I
Shepro
D
D
Hechtman
H B
HB
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D001998:Bronchopulmonary Sequestration / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury; D004487:Edema / Q000139:chemically induced* / Q000503:physiopathology; D007376:Interleukin-2 / Q000494:pharmacology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology; D007958:Leukocyte Count / Q000187:drug effects; D007970:Leukopenia / Q000139:chemically induced; D008107:Liver Diseases / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010976:Platelet Count / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood
D007376:Interleukin-2; D011994:Recombinant Proteins; D013929:Thromboxane B2