• INCLUSION CRITERIA:

To be eligible for this protocol, a patient must meet the following five criteria:

Diagnosed with M. avium complex (MAC) lung disease or other pulmonary mycobacterial infection based on the 1997 version of American Thoracic Society (ATS) diagnostic criteria and have positive AFB smear or culture for mycobacterial infection at least three months prior to the date of enrollment. Patients with only histological evidence of mycobacterial infection without positive smear or culture will not qualify for this protocol even if they meet the ATS diagnostic criteria for nontuberculous mycobacterial lung infection.

A patient must have radiographic evidence on high resolution computerized tomography of changes that are consistent with pulmonary mycobacterial infection. These include, but are not limited to: multiple small nodules (less than 5 mm), and cylindrical bronchiectasis.

The patient must be on a treatment regimen based on ATS guidelines that has been stable for at least three months. By stable, we mean that the patient has been tolerating the regimen without any significant adverse reactions, and that no new agents have been begun in the last three months.

The patient must be female and can be post-menopausal (either through natural menopause or surgical removal of her ovaries) or menstruating. If the patient is still menstruating and randomized to a study group receiving a cytokine she must agree to monthly pregnancy testing, while on study, as well as to utilizing a barrier type of contraception or abstinence. She must not be under 40 years of age at the time of enrollment in the study.

The patient must be enrolled in protocol # 01-I-0202 ("Natural History, Genetics, Phenotype, and Treatment of Non-Tuberculoid Mycobacterial Infections").

EXCLUSION CRITERIA:

Patients with pulmonary MAC disease who do not meet the above entry criteria.

Patients with any of the following preexisting medical conditions:

1. HIV positive
2. asthma
3. active cancer requiring treatment
4. hepatic disease (defined as either a history of cirrhosis, or grade 3 or 4 hepatic toxicity by the Toxicity Table in Appendix II)

Patients who are unable to tolerate bronchoscopy. This will be defined by the following criteria:

1. A pulse oximetry reading less than 100% when given supplemental oxygen at 100% FiO2.
2. Clinically significant reactive airway disease that does not respond to bronchodilators.

Patients with the following laboratory abnormalities:

1. creatinine greater than 1.5 mg/dL
2. Hemoglobin less than 9 mg/dL
3. WBC less than 3,000
4. Platelets less than 150,000
5. ALT greater than 82 U/L, or AST greater than 78 U/L.
6. Bilirubin greater than 2.0 mg/dL
7. Alkaline phosphates greater than 232 U/L

Patients with a preexisting allergy or history of allergic reactions to study or protocol medications. These include, but are not necessarily limited to: IFN-gamma, GM-CSF, azithromycin/ clarithromycin, ethambutol, rifampin/ rifabutin, anesthetic agents employed in bronchoscopy, or any yeast-derived products.

Patients who are unable to maintain the described follow up schedule. Likewise, patients who are unable to give informed consent are excluded from the study.

Patients with clinical diagnosis of cystic fibrosis.

Patients who are either currently smoking, or have a previous history of smoking that exceeds 20 pack years.

Patients with prior treatment with either IFN-gamma or GM-CSF within the last three months.

Patients with known history of cardiac, endocrine, neurologic or other medical conditions that the principal investigator deems dangerous or unsuitable for enrollment will be excluded.

Patients who are either pregnant or lactating. Also, menstruating patients who are randomized to a study group receiving a cytokine and refuse to use appropriate barrier forms of contraception or abstinence during this trial be excluded.

Patients who, at any time during this trial, have an active lung infection caused by either Staphylococcus or a gram negative rod are excluded from this trial until this infection has been successfully treated.

Patients that need to use supplemental oxygen.

Patients who have a Forced Vital Capacity less than 40% predicted.

Patients who are unable to walk and participate in the 6MWT.