Interleukin-2 inhalation therapy temporarily induces asthma-like airway inflammation.
BACKGROUND
Inhaled interleukin-2 (IL-2) is an effective and safe treatment in metastasing renal cell carcinoma (mRCC) but known to potentially elicit respiratory symptoms.


OBJECTIVE
The present study analyses the effects of IL-2 using a panel of measures including markers of airway inflammation.


METHODS
Ten patients with mRCC (7m/3f; mean age, 63 yrs) were measured at baseline, 6-10 days after start of therapy (n = 5, inhaled IL-2 only; n = 5, inhaled IL-2 plus 1/11th of daily dose subcutaneously), and 16-29 days later under continuous combined (inhaled plus subcutaneous) therapy, including additional subcutaneous IFN-alpha in 8 patients.


RESULTS
After start of therapy median FEV1 declined from 108 to 85 to 90 % predicted and the provocative concentration of methacholine eliciting a 20 % fall in FEV1 (PC20 FEV1) from 16 to 8 to 3 mg/mL, while the level of exhaled nitric oxide (FENO) rose from 27 to 79 to 60 ppb and the percentage of sputum eosinophils from 2 to 18 to 37 % (p<0.01, each), accompanied by cough and dyspnoea (p<0.05). One patient who stopped therapy, was back to baseline values when measured 2 months later. Cytokine production by blood or sputum T lymphocytes was not markedly altered by IL-2 inhalation.


CONCLUSIONS
IL-2 inhalation therapy in patients with metastasing renal cell carcinoma is capable of temporarily inducing symptomatic, functional and inflammatory alterations similar to those of bronchial asthma.
Loppow
D
D
Research Laboratory, Hospital Grosshansdorf, Center for Pneumology and Thoracic Surgery, Grosshansdorf, Germany.
Huland
E
E
Heinzer
H
H
Grönke
L
L
Magnussen
H
H
Holz
O
O
Jörres
Rudolf A
RA
D000280:Administration, Inhalation; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D001944:Breath Tests; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy* / Q000556:secondary; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012129:Respiratory Function Tests; D013183:Sputum / Q000166:cytology / Q000378:metabolism
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D009569:Nitric Oxide; C082598:aldesleukin