Effects of Nebulized Alpha-2-Macroglobulin in Adult, Asthmatic Horses

Abstract: Background – Given the broad anti-inflammatory actions of alpha-2-macroglobulin (A2M) in other body systems, investigation into the safety and clinical effects of nebulized A2M in horses as a potential adjunctive management approach for equine asthma warrants consideration. Objectives/Hypothesis – To evaluate the effects of nebulized A2M on clinical signs, lower respiratory tract inflammation, and pulmonary and systemic cytokine concentrations in asthmatic horses. It was hypothesized that effects of A2M would not differ from nebulized saline. Animals – Thirteen university-owned adult, asthmatic horses. Methods – Enrolled horses were randomly divided into two groups. The A2M group received nebulized A2M suspension every 48 hours for 6 doses, while the SALINE group received nebulized saline at matching timepoints. Vital parameters and a 23-point respiratory score were assessed by a blinded veterinarian before each treatment and 24h after the last treatment. Rebreathing examinations, bronchoalveolar lavage fluid (BALF) for cytology and cytokine analysis, and blood for cytokine concentration were collected before the first and 24h after the last treatment. Results – There were no significant differences in clinical respiratory scores in the A2M group throughout the study, while the SALINE group had increased scores on days 2, 6, and 8. BALF inflammatory cell percentages and cytokine concentrations in both BALF and serum showed no significant differences between groups at any time. Conclusions and Clinical Importance – Nebulized A2M was well tolerated and did not exacerbate clinical signs in horses with mild asthma. Further investigation into dosing regimens and effects on more severe disease is warranted.