Gamma Interferon Induced Organ Regeneration

Discussion

The currently available treatments for pulmonary fibrosis have not been shown to improve survival or to substantially improve lung function in well-designed multicenter, large clinical trials [7,9]. Moreover, these “standard” treatments which utilize corticosteroids and other immunosuppressants may increase morbidity and decrease quality of life and contribute to an increased risk of life threatening infection.

The subsets of patients who have extensive UIP disease are particularly difficult to treat [7,9]. Advanced age further worsens the prognosis in these patients. The patient’s prognosis at the time of diagnosis was poor with an estimated life expectancy of 1-2 years and probable evolution to a need for home oxygen therapy within months. I was able to administer suprapharmacologic doses of IFN-gamma-1b directly into the lung with no substantial toxicity and few side effects to the patient. The doses are 10-25 fold greater than those used in other studies of this drug in humans, yet I have seen fewer side effects than would be expected, even when compared to the lower doses.

I have designed a sequential treatment regime escalating to very high dose inhaled IFN-gamma-1b plus HDIVIG which resulted in probable regeneration of functional alveoli. Regeneration of organs in adult humans, except for some potential for liver regeneration, has not been previously shown.

This patient had advanced UIP and had already lost much of his lung to the fibrotic (scarring) process. The loss of lung function was well documented by history, physical examination, multiple pulmonary function tests, multiple chest x-rays, an adequate two-specimen lung biopsy, and two high resolution CT scans. It is unheard of for such a patient to regain almost all his lung function (see Table 2) after it had been turned to “scar.” I believe the only explanation for the dramatic results seen in the patient is that the therapy shut off the autoimmune and/or fibrotic response and induced regeneration of new lung parenchyma and probably new alveoli.

The patient required long term treatment with gamma interferon. I suspect that the scarred lung parenchyma needed to undergo collagen remodeling and in the gamma interferon induced milieu new lung parenchyma, including alveoli, developed. Shorter term gamma interferon administration might be sufficient if scarring (fibrosis) has not already developed.

Interestingly, the patient, despite being gray for 25 years has regained some blond hair pigment and has regrown almost all of his hair. This may represent hair follicle stem cell induction.

These very preliminary data suggest reversion, at least partially, to an embryonic developmental state at two sites, the lung and scalp.

Although the preliminary data in this report deals with lung regeneration, I believe that by delivering very high dose gamma interferon to other organs or tissues it may be possible to induce a regenerative response.

For example, in the case of an amputated digit the damaged end can be treated with a polymeric scaffold decorated with gamma interferon.

Treatment of the heart can use the same inhalational protocol described herein. Treatment of other organs can be accomplished via continuous infusion of gamma interferon via the arteries feeding the target organ.