in vivo 22 : 263-268 (2008) Short Review Control of Interstitial Pneumonia by Drip Infusion of Megadose Vitamin C, Dehydroepiandrosterone and Cortisol. A Short Review of our Experience MITSUO KODAMA 1, ATSUSHI OYAMA 2 and HIROSHI TAKAGI 3 1Kodama Research Institute of Preventive Medicine, 2Hikarigaoka Clinic, and 3Second Department of Surgery, Nagoya University School of Medicine, Nagoya, Japan Abstract. Interstitial pneumonia can be controlled by the granulatory tissue (1). The interstitial tissues are also combined use of a prophylactic antibiotic system and the drip involved in the site of granulation (1). All these descriptions infusion system including megadose vitamin C, dehydro- are in good agreement with the pathological changes of epiandrosterone (D) and cortisol (F), a fortified substitute of 3 interstitial pneumonia (2). In the treatment section, adrenocortical elements. The response of patients was satisfying Heilmeyer warned of the possible emergence of antibiotic with few side-effects of F. It was shown that an excess of resistance in local bacteria (1). Eventually, cortisone and vitamin C improved the therapeutic efficacy of D-F complex, adrenocorticotropic hormone (ACTH) could be tried under and that D and F improved the immunodeficient state of the the antibiotic protection (1). Above all, attention should be host. The benefit of D as an adrenal androgen in immunology directed to the control of both the heart and the general found another example in the combined use of cyclosporine A circulation system (1). With the use of cortisone and ACTH, (CS) and glucocorticoid (G) in the kidney transplantation Heilmeyer might have been inspired by the opinion of a clinic: CS and G helps improve graft take by creating a state of group of researchers that his chronic pneumonia might androgen excess, as testified in both humans and mice – an respond to a beneficial action of glucocorticoid, as is the alleviation of immune conflict. case in arthritis and nephritis (1). In 1962, an article on interstitial pneumonia was presented in Harrison Principles Chronological Transition of Disease Concept in of Internal medicine under the name of chronic bronchitis Interstitial Pneumonia and emphysema(3). Knowles emphasized the significance of this disease with a remark as follows: “In England it is the In 1957, Heilmeyer pointed out that a variety of infectious commonest cause of death and morbidity among all diseases might trigger the onset of his “chronische respiratory diseases, including pneumonia, tuberculosis, Pneumonien”, a finding to suggest that the disease may not asthma and lung cancer” (3). be aetiologically a specific entity. He also added that a As to the treatment, Robin also expressed rather a group of researchers had noted the primary character of negatine opinion (4) thus: “a diagnostic and therapeutic these phenomena (chronic pneumonias) (1). In the course trial with corticosteroids (C) may be indicated. Careful of the lung infiltration, one sees microscopically the evaluation by serial test is necessary to determine the development of connective tissues and capillaries from the ultimate need for such therapy. Early and vigorous walls of bronchioles and the occupation of alveoli by chemotherapy is important. Less well established is the use of prophylactic chemotherapy during infection-free periods. This problem is currently under study” (4). He expected the role of C to be that of a bronchial dilator alone (4). Knowles Correspondence to: Dr. Mitsuo Kodama, Kodama Research states that “roentgenography is of little help in diagnosis Institute of Preventive Medicine, 3-108 Gardenhills, Fujimidai 4- until the disease is advanced” (3). 1, Chikusa-ku, Nagoya 464-0015, Japan. The next Harrison Book, 11th edition published in 1987, Key Words: Interstitial pneumonia, drip infusion, megadose vitamin makes a sharp contrast in many respects to the 4th edition: C, dehydroepiandrosterone, cortisol, fortified adrenocortical firstly the new book presented a beautiful X-ray image of elements, short review . interstitial pneumonia of an early stage, in which a linear or 0258-851X/2008 $2.00+.40 263 in vivo 22 : 263-268 (2008) reticular pattern involves the lower lung fields bilaterally, the people showed increased blood levels of 17- more on the right (2). Secondly, the book shows that the hydroxycorticoids (17-OHCS) after this vitamin condition is an autoimmune disease of which the emergence supplementation. The ascorbic acid loading also raised their is often associated with concomittant eruption of other urinary output of 17-ketosteroids (17-KS) and intensified autoimmune disorders (2). In contrast to the 4th edition, their response to ACTH, as judged by the eosinopenic effect chest X rays test show abnormalities in the lung parenchyma and by the effect on their production of steroid hormones in 90% of cases in the posteroanterior and lateral image (2). (7). It is now asked whether or not a deficiency state of Thirdly, “specific therapy for most of the interstitial lung vitamin C and adrenal steroids is the sine qua non condition disorder (ILD) is directed toward suppressing the of autoimmune disease and/or aging. As regards the adrenal inflammatory process in the lower respiratory tract. steroids, one should keep in mind that the adrenal cortex, Typically, oral corticoscosteroids are used starting with a when stimulated by ACTH, increases secretion of both high dose (usually 1 mg/kg of prednisone daily) for 4 to 6 glucocorticoids and D, the latter being an adrenal androgen weeks and then gradually tapering to a low maintenance which comes from the zona reticularis and zona fasticulata dose (0.25 mg/kg of prednisone). If the disease is of the adrenal cortex (8). Similar responses of 2 steroids to suppressed, no therapy” (2). The opinion of King in the ACTH strongly suggest the possibility that F and D may be 15th edition published in 2001, again sounds rather functionally interrelated with each other. Furthermore, the negative. He says that, in the case of idiopathic pulmonary administration of ACTH causes glucocorticoid secretion fibrosis, “the clinical course is variable with a 5-year survival and a rapid and profound but temporary depression in the rate of 30 to 50% after diagnosis” and that “there is no firm vitamin C content in the adrenals of rats, guinea pigs, and evidence that any of these treatment approaches improves other animals (7). Evidence is available to indicate that survival or the quality of life” (5). The presented X-ray ACTH causes both an accelerated uptake and release of image of interstitial pneumonia does not serve as a guide to vitamin C by the adrenals (9). All these observations in the readers who want to diagnose the disease at an early experimental animals are in good agreement with the stage, since the image in this book belongs to an advanced vitamin C loading study in Russia (7). It will be pertinent to stage of the disease. recall the well-known fact of immunology that D can significantly prolong the lifespan of (NZBxW) F1 females The Significance of Vitamin C and Adrenal Steroids with the murine model of systemic lupus erythematosus as immunomodifiers in Immunological Disease (SLE) (10). Drip Infusion System of Megadose Vitamin C and In 1989, Clemetson reported a case in which he took 5 Adrenal Steroids in the Treatment of Autoimmune blood samples from a 19 year old Irish woman who was Disease critically ill with a reccurence of rheumatic fever, having excessive vaginal bleeding (6). Clemetson investigated the Our study with the drip infusion of vitamin C for diabetes plasma contents of total ascorbic acid (TAA), reduced form mellitus (DM) was started in 1992 using 7 g of vitamin C ascorbic acid (AA), and dehydroascorbic acid (DHAA) with and 25 g of glucose dissolved in 500 ml water solvent as the 5 blood samples before, during and after prednisone drip infusion set (11). Results obtained are as follows: i) the treatment. The ratios of AA to DHAA were as follows: i) plasma concentration of insulin revealed two surges, each 7 0.9:1 (before); ii) 0.8:1 (before); iii) 3.2:1 (5th day on minutes and 2 hours after the start of drip infusion, a prednisone); iv) 1.8:1 (after prednisone); v) 2.3:1 finding indicating that two distinct mechanisms are in action (convalescent). For reference, the mean ratio for 5 healthy with the promotion of plasma insulin by vitamin C infusion. nurses was 7.2:1 (6). It was indicated that her rheumatic ii) Distinct clinical improvements were observed with the fever required the supply of both vitamin C and long-term use of vitamin C infusion in 3 DM patients (11). corticosteroid for its cure (6). At the time of convalescence, Next, the drip infusion of similar megadose vitamin C was her vitamin C content (TAA) was 7.2, a value which was tested as regards its effect on plasma cortisol (F). Results much lower than the normal figure of 12.3 (6). Clemetson obtained are as follows: i) the plasma F concentration cited another example of vitamin C supplementation in the increased 2 hours after vitamin C infusion. The same elderly population in Russia. A total of 144 elderly men and treatment also enhanced diuresis and excretion of urinary women (aged 60 to 90 years) were subjected to a vitamin C 17-OHCS, as tested in a healthy male volunteer. i i) Distinct study at the Leningrad Medical Institute of Sanitation and clinical improvements were observed in 4 patients with Hygiene for healthy old people. It was reported that autoimmune diseases (two cases of rheumatoid arthritis, ascorbic acid loading (500 mg daily for 12 to 14 days) one case of nephritis-linked hypertension and one case of improved the functional state of the adrenal cortex; 70% of hepatic dysfunction) (12). 264 Kodama et al : Dehydroepiandrosterone and Pneumonia ( Short Review ) We then investigated the relation between ACTH, F and The time distribution of the above 313 patients covered the vitamin C in plasma in the course of vitamin C infusion range from January to December of 1995, leaving a few treatment with and without the use of methylprednisolone, spill-overs in 1994 (15).