Interleukin-2 inhalation therapy temporarily induces asthma-like airway inflammation

Inhaled interleukin-2 (IL-2) is an effective and safe treatment in metastasing renal cell carcinoma (mRCC) but known to potentially elicit respiratory symptoms.

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

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.

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.

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.