Administration Of Cortisone Research Articles

Glucocorticoids and dietary iron regulate postnatal intestinal heavy and light ferritin expression in rats.

To cope with increasing dietary iron exposure, the intestinal epithelium of weaning rats must control intracellular labile iron pools. Intestinal expression of heavy (H) and light (L) ferritin subunits during early weaning and after cortisone administration and/or iron feeding was investigated. Changes in H and L ferritin gene expression were determined by nuclear runoff transcriptional assay, Northern blot analysis, and metabolic labeling of protein synthesis. H ferritin mRNA levels did not change between days 12 and 15, doubled on day 18, and tripled on day 24. L ferritin mRNA was reduced by 50% on days 18 and 24. The protein level of the H and L subunits paralleled the change in mRNAs. Cortisone treatment on day 12 induced a precocious increase of H and decrease of L mRNA expression on day 15. Nuclear runoff assays showed that cortisone did not change H and reduced L ferritin gene transcription. The increased level of H mRNA by cortisone was not translated, unless the rats were fed an iron-fortified diet, which reduced iron regulatory protein activity and stimulated a three- to sixfold increase of ferritin synthesis. Thus changes in intestinal H and L ferritin expression in weaning rats are modulated by glucocorticoids and iron; the former stabilizes H mRNA and suppresses L ferritin gene transcription, and the latter derepresses translation of ferritin mRNA.

Progestogens: Thrombosis and Osteoporosis

Observations on osteoporosis from the sixth century onwards have shown that stress is the main causative factor. This has been confirmed by animal experiments, using rabbits, with stress simulated by the administration of cortisone. For normal health, the hormonal anticatabolic/catabolic ratio should remain on the anticatabolic side. Stress, emotional or otherwise, can tip the balance over to the catabolic side. In the presence of progestational compounds (in the pill or hormone replacement therapy), much lower levels of stress are needed. The main types of osteoporosis are disuse, with a lower blood flow through bone, steroid-induced and thrombus-induced osteoporosis. When the anticatabolic/catabolic ratio tips to the catabolic side, cell membranes become more rigid. Osteogenic precursor cells coalesce to form osteoclasts, which remove bone. Memory cells are affected, and also those responsible for the absorption of food from the gut. Increased catabolic levels also lead to the production of abnormal meg...

CT-guided intraarticular corticosteroid injection into the sacroiliac joints in patients with spondyloarthropathy: indication and follow-up with contrast-enhanced MRI.

Our goal was to prospectively study the therapeutic efficacy of CT-guided intraarticular corticosteroid instillation of inflamed sacroiliac joints (SIJs) in patients with spondyloarthropathies and to evaluate the role of MRI as a procedure for establishing the indication and for therapeutic follow-up. A total of 103 CT-guided corticosteroid injections of the SIJs were performed in 66 patients with inflammatory back pain (IBP): 37 bilateral, 29 unilateral. All patients did not respond to an immediately preceding 4 week nonsteroidal antiinflammatory therapy. Forty milligrams of a crystalline long-acting corticoid was instilled in each joint. All 66 patients underwent continuous clinical follow-up at 10 to 12 week intervals after corticosteroid injection to a maximum of 18 months. The degree of subjective complaints before and after the intervention was recorded using a analogue scale (0 = no pain, 10 = unbearable pain). Dynamic contrast-enhanced (Gd-DTPA, 0.1 mmol/kg body wt) MRI with quantitative determination of contrast enhancement was performed in all patients before the therapeutic intervention and in 38 patients at 8 +/- 4 months. Sixty-one of the 66 study patients (92.5%) showed a statistically significant abatement of subjective complaints from 8.8 +/- 1.3 to 3.3 +/- 2.3 (p < 0.01) at 1.7 +/- 1.1 weeks after intervention, and this improvement lasted for 10 +/- 5 months. The percentage contrast enhancement at dynamic MRI likewise showed a significant reduction from 100.3 +/- 48% before to 44.3 +/- 36.1% after intraarticular cortisone administration (p < 0.01). CT-guided intraarticular corticosteroid instillation in the SIJs may be regarded as an effective therapy for florid sacroiliitis. The severity of inflammation and the response to therapy can be determined quantitatively by dynamic MRI.

Technetium-99m pentavalent dimercaptosuccinic acid imaging in patients with pituitary adenomas

We studied the tumor-seeking agent technetium-99m-labeled pentavalent dimercaptosuccinic acid ([99mTc](V)DMSA) to visualize 21 growth hormone (GH)-, nine prolactin (PRL)-, two mixed GH/PRL-, six adrenocorticotrophin (ACTH)-secreting and 15 clinically non-functioning pituitary adenomas, three craniopharyngiomas and one dysgerminoma of the sella. All non-adenomas and 31 out of 53 adenomas were studied before treatment: 22 after surgery and/or radiotherapy. Eight cases of acromegaly were studied before and after chronic treatment with octreotide, whereas three cases of acromegaly, one of prolactinoma and two of non-functioning adenoma were imaged before and after adenomectomy. As a control group, 27 patients without any clinical evidence of pituitary adenoma were studied: 10 of them were operated on previously and treated with iodine-131 for metastatic thyroid carcinoma, 10 had brain tumors and the remaining seven patients had functional pituitary hypersecretion (four Klinefelter's syndrome, two primary hypothyroidism and one Addison's disease). The scintigraphy was repeated after testosterone in Klinefelter's syndrome, L-thyroxine in primary hypothyroidism and cortisone administration in Addison's disease. Seventeen GH-secreting (81%), seven PRL-secreting (78%), three ACTH-secreting (50%), 15 non-functioning (100%) and one (50%) mixed adenoma significantly concentrated [99mTc](V)DMSA, showing elevated tumor-to-background (T/B) ratios. The T/B ratios were similar in untreated and surgically treated adenomas (11.2 +/- 5.6 vs 11.8 +/- 6.2). Radiotherapy significantly lowered the [99mTc](V)DMSA uptake to 5.1 +/- 2.8 (p < 0.1 vs untreated patients). Non-adenomatous lesions of the sella turcica did not concentrate [99mTc](V)DMSA in the pituitary as well as brain tumors and 8 out of 10 metastatic thyroid cancers. The treatment with octreotide normalized GH and insulin-like growth factor I levels and reduced [99mTc](V)DMSA from 15.7 +/- 4.8 to 13.5 +/- 3.9 (p < 0.05). Conversely, adequate substitutive therapy completely inhibited the uptake of the radiotracer in Klinefelter's syndrome, in primary hypothyroidism and in Addison's disease. The [99mTc](V)DMSA scintigraphy showed an overall sensitivity of 81% (43/53) in detecting pituitary adenomas, which was increased to 95% for lesions greater than 10 mm in size. High-quality images with minimal total body radiation were obtained, enabling a good in vivo characterization of viable adenomatous tissue as well as an accurate monitoring of the effects of different therapeutic regimens.

Development and hormonal modulation of postnatal expression of intestinal alkaline phosphatase mRNA species and their encoded isoenzymes

In the rat, intestinal alkaline phosphatase (IAP) activity in the duodenum, but not jejunum, increases on day 22-24 after birth and exhibits higher activity hydrolysing phenyl phosphate (PhP) than beta-glycerophosphate (beta GP) [Moog and Yeh (1973) Comp. Biochem. Physiol. 44B, 657-666]. The mechanism underlying these developmental changes remains unknown. To define possible mechanisms, we have measured IAP activity and mRNA levels, and analysed IAP mRNA species and isoenzymes on postnatal days 12, 18, 24 and 32. Duodenal IAP activity and mRNA content were identical on postnatal days 12 and 18, but were 7-fold and 3-fold higher on day 24, respectively than on day 18. The increased IAP activity exhibited a high PhP/beta GP ratio and was accompanied by initial appearance of the 3.0 kb mRNA and 90 kDa isoenzyme. On day 32, duodenal IAP activity did not increase over the levels on day 24, whereas mRNA levels doubled. The lack of enzyme increase might be related in part to increased apical release, as luminal IAP activity increased from 2% of total mucosal IAP on days 12 and 18 to 7% and 14% on days 24 and 32 respectively. In the jejunum, IAP activity decreased postnatally, but mRNA content was unaltered; only the 2.7 kb mRNA and 65 kDa IAP isoenzyme were present. Administration of cortisone or cortisone+thyroxine induced simultaneous appearance of the duodenal 3.0 kb mRNA and 90 kDa isoenzyme with an increased PhP/beta GP ratio. Thus postnatal increase in duodenal IAP activity is related to the expression of a 90 kDa PhP-preferring isoenzyme encoded by the 3.0 kb mRNA. The low-PhP/beta GP-ratio 65 kDa isoenzyme is expressed in the duodenum and in the jejunum and is encoded by the 2.7 kb mRNA.

Factors Affecting Circulating Growth Hormone Binding Protein in Chickens

Growth hormone binding protein (GHBP) may be an important factor in the regulation of growth and might provide an indirect, relatively noninvasive means of predicting the status of hepatic growth hormone receptor (GHR) activity. Several factors have been reported to influence growth hormone (GH), GHR, or GHBP. Therefore, these studies were conducted to test how age, sex, nutritional status, and glucocorticoids (cortisone acetate, CA) influence serum concentrations of chicken GHBP. Serum GHBP activity was highest (mean percentage specific binding (%SB) = 12.43 ± .80) at hatch and decreased linearly (P < .0001) to 5 wk of age (%SB = 1.99 ± 1.13). There were no sex-related differences in serum GHBP activity from hatch to 5 wk of age (P > .08). Short-term nutrient deprivation (24-h) of 4-wk-old broilers also had a significant effect on serum GHBP activity (P < .0001). Measurement of serum GHBP activity with refeeding (after a 24-h period without feed) restored %SB to normal values. Feeding broilers a low-protein diet (12% CP) did not significantly affect serum GHBP activity when compared with that of broilers fed a commercial broiler diet (23% CP; P > .30). Administration of cortisone (1, 5, and 10 mg/day), every 24 h for 7 days, had no effect, at any dose, on serum GHBP activity at 48 h and 1 wk after the last injection. These results indicate that serum GHBP activity is influenced by factors such as age and feed deprivation. It remains to be determined whether these changes in GHBP are associated with changes in GHR as reported for mammalian species.

A survey of postoperative steroid replacement in 40 patients with Cushing's syndrome

Adrenalectomy for Cushing's syndrome due to adrenocortical adenoma was performed on 40 patients at Tokyo University Hospital between 1960 and 1990. There were 32 women and 8 men aged 2 to 59 (mean 35.7) years. Three different operative approaches to the adrenal gland were employed: lumbar approach in 24 cases, dorsal in 8, and transabdominal in 8 of whom 7 patients were operated before 1970 without definite preoperative localization of the lesions. Postoperative administration of cortisone and hydrocortisone as a steroid replacement has been reduced in duration and dosage in recent 10 years. Average treatment period was 3 years and 1 month in the 1970's, and 9.5 months in the 1980's, respectively. The mean daily dosage of steroid hormone was 517.5 mg (mean) on the operative day and 43.1 mg after three weeks in the 1970's, while 187.5 mg and 18.4 mg in the recent five years, respectively. Nonetheless, even in the recent 6 patients, metabolic alkalosis and hypopotassemia because of steroid excess were observed in a few days after the surgery. These observations indicate that period and dosage of steroid replacement have been reduced in these years and could be further shortened by means of rapid tapering in the early postoperative phase.

Modulation of sleep by cortisone in normal and bacterially infected rabbits

Infectious disease is known to alter both sleep patterns and hydrocortisone (cortisol) concentrations in rabbits. Moreover, the sleep-altering effects of microbial infections are likely to be mediated via endogenous immune modulators whose actions are attenuated by glucocorticoids. To evaluate the relationships between sleep and glucocorticoids during infectious disease, the effects of cortisone administration (20 mg/kg, im) on sleep were examined before and after inoculation of rabbits with Staphylococcus aureus or Escherichia coli. When administered alone, cortisone did not alter the amount of time spent in slow-wave sleep (SWS) but did reduce electroencephalographic (EEG) slow-wave amplitudes during SWS, the number of bouts of SWS and the amount of time spent in rapid-eye-movement sleep. The duration of individual bouts of SWS was increased after cortisone treatment. Bacterially infected rabbits developed biphasic changes in sleep patterns that were characterized by an initial increase and a subsequent decrease both in SWS time and in EEG slow-wave amplitudes during sleep. Cortisone treatment attenuated these effects in S. aureus-inoculated rabbits. In contrast, cortisone treatment did not alter the initial phase of enhanced sleep in E. coli-inoculated rabbits but did attenuate the subsequent sleep suppression. These data indicate that glucocorticoid administration is associated with an attenuated sleep response in bacterially inoculated rabbits.

Detection of Fc receptors for IgA on rat alveolar and peritoneal macrophages

The presence of Fc receptors for IgA on alveolar macrophages was determined by rosette assay and immunogold labeling. IgA-mediated phagocytosis by alveolar macrophages was observed. Results of these assays were compared between rats receiving no treatment and those receiving long-term cortisone administration. Sheep erythrocytes coated with dextran and an IgA monoclonal antibody specific for the α 1,3 linkages of dextran bound to 16% of alveolar macrophages. However, peritoneal macrophages did not form rosettes with dextran-IgA-coated erythrocytes. Immunogold labeling by transmission electron microscopy revealed that most Fc receptors for IgA were found on the membrane of pseudopodia of activated alveolar macrophages. Long-term cortisone administration diminished the phagocytosis and phagocytic index of alveolar macrophages, thereby contributing to decreased host resistance to infection (e.g., Pneumocystis carinii pneumonia).

Effects of prenatal administration of testosterone and cortisone on the reproductive system of the female rat

Testosterone propionate, cortisone, or sesame oil vehicle were given to rats during the last week of pregnancy so that effects of the hormones on anogenital distance, breeding capacity and vaginal opening of the female progeny could be contrasted. Testosterone significantly increased anogenital distance and delayed vaginal opening of progeny. When females that had been exposed to testosterone in utero were tested for breeding capacity, a significantly smaller number mated than in the control group. Female rats that had been exposed to cortisone in utero exhibited premature vaginal opening but did not differ from controls in anogenital distance, and, unlike the testosterone-exposed rats, mated. Cortisone-exposed rats carried litters to term and the litters did not differ from those of controls in numbers of pups or numbers of living pups at birth. The pups born to cortisone-exposed rats had greater birth weights and a higher survival rate to 20 days of age than pups of controls. Results indicate that testosterone administration to rats during pregnancy is far more detrimental to the development and subsequent function of the reproductive system of female progeny than cortisone and suggest that similar changes which occur in response to maternal stress or to administration of ACTH during pregnancy are more likely to result from increases in testosterone than from increases in glucocorticoid secretion.

Response of pre-adult and adult stages of Trichuris muris to common anthelmintics in mice

The common anthelmintics, oxantel, mebendazole, albendazole and pyrantel were assessed for their comparative activity against Trichuris muris in mice. Mice were infected with T. muris and the infection was maintained by a brief cortisone administration during the second week of infection. Mice carrying the infection with different life cycle stages, viz. fourth stage larvae (L4), pre-adult and adult stages were dosed with anthelmintics. The worm burdens in control infection groups varied although infection dose and other conditions were uniformly followed. With various dose regimens tested, oxantel was highly potent; it eliminated completely pre-adult and adult stages, respectively at 25 and 12.5 mg kg −1 dose levels with significant activity also against adult worms at a 1.56 mg kg −1 dose level and against preadults at a 6.25 mg kg −1 level. Pre-adults required twice the dose given to that of adults for complete (100%) activity. Mebendazole was the next most active; a dosage of 37.5 mg kg −1 was completely active against preadults whereas a dosage of 2 × 50 mg kg −1 was required for complete elimination of adult worms. In addition, about 90% of the worms were eliminated with a single dose of 150 mg kg −1. However, a significant activity was seen against adults at a 25 mg kg −1 level and pre-adults at 37.5 mg kg −1, the lowest level tested. In comparison, albendazole did not induce complete clearance of pre-adult and adult stages even when tested at dose levels as high as 150 and 2 × 75 mg kg −1, respectively. All anthelmintics were completely effective (100% activity) against L4 even with the lowest dose (oxantel 6.25 mg kg −1; mebendazole and albendazole 37.5 mg kg −1) tested. Pyrantel showed a very insignificant activity. Experimental data show that the conditions prevailing in the infected host are important for exerting anti-parasite activity.

Effect of Malnutrition and Hormone Treatments on Intestinal Microvillus Membrane Glycosylation in Suckling Rats

Imposition of undernutrition in suckling rats significantly enhanced (p less than 0.001) sialic acid and reduced (p less than 0.001) fucose contents of intestinal microvillus membranes (MVM) compared to the controls. Administration of cortisone or insulin to undernourished (UN) pups reversed the sialylation and fucosylation pattern of the membranes. The binding of wheat germ agglutinin (WGA) to membranes was increased (p less than 0.001) and that of Ulex europeus agglutinin (UEA) was decreased in nutritionally deprived pups. Cortisone and insulin treatments reduced WGA and enhanced UEA bindings to UN membranes. The binding of peanut agglutinin (PNA) to UN membranes was 60% higher compared to that in the control rats. Cortisone and insulin treatments further enhanced PNA binding to the brush borders in UN pups. The incorporation of 14C-GlcNAc, 14C-mannose and 3H-fucose into MVM was reduced by 32-57% in UN suckling rats compared to the controls. The incorporation of labelled sugars into membranes from 21- and 50- to 60-day-old rats was essentially similar. Cortisone administration to UN pups augmented the incorporation of labelled GlcNAc and mannose but had no effect on fucose incorporation. Insulin treatment of UN pups insignificantly elevated GlcNAc incorporation into the membranes. These findings suggest that imposition of UN during early suckling period delays the maturational development of intestinal glycosylation. Cortisone and insulin induced adult-type glycosylation pattern of the brush borders in nutritionally deprived pups.

Modulation of growth of melanoma.

Combined heparin-cortisone treatment induces regression of growth in a variety of murine tumors including melanoma. We injected 92 inbred C 57 b1/6 male mice each with 5 X 10(5) melanoma cells (B16, B16 F1, and B16 A6 lines) with different metastatic potential. Heparin (400 U/ml) and cortisone acetate (250 mg/kg SC injections) were given daily. Control experiments were performed both with the administration of no drugs and with administration of cortisone alone. Plasminogen activator activity, which is notoriously related to tumor growth, was evaluated using fibrin plate technique in 10 fragments taken before and 20 days after the combined heparin-cortisone treatment of B16 F1 and B16 A6 melanomas. The combined heparin-cortisone treatment slowed tumor growth, but no tumour regression was observed. Cutaneous fibrinolytic activity appeared increased in all specimens after the treatment.

Changes in sialic acid and fucose contents of enterocytes across the crypt-villus axis in developing rat intestine

Alterations in sialic acid and fucose contents of different populations of epithelial cells have been studied in suckling and adult rat intestine. The progression of cells from crypt base to villus tip is associated with an increase in sialic acid and a decrease in fucose levels of the cells in adult rats. In suckling pups, sialic acid is uniformly distributed along the length of villi, and fucose is richly ( P < 0.01) present in cryptic cells compared to that at the villus tip. Adult-type changes in sialylation and fucosylation of enterocytes across the crypt-villus axis were precociously produced by cortisone administration to suckling pups. Thyroxine treatment was less effective in influencing the glycosylation process in rat intestine.

Trichinella spiralis: Differences between “early” and “late” rapid expulsion evident from inhibition studies using cortisone and irradiation

Cortisone administered once at 100 mg/kg during the first 3 weeks of infection inhibited rapid expulsion. In rats immunized with an abbreviated infection ( T M regime) inhibition averaged approximately 50%, whereas in rats given a complete infection (C.I.) 14% inhibition occurred. Sensitivity to 400 rad whole-body irradiation was greatest 7 days before a challenge infection in all immune rats. Three days after beginning the T M infection rats were highly susceptible to cortisone but only weakly so to irradiation. Rats immunized by C.I. were equally, but only weakly, susceptible to either cortisone or irradiation 3 days after infection. Acute administration of cortisone 1 or 4 hr prior to challenge did not inhibit rapid expulsion but 60% inhibition occurred when cortisone was given 24 hr prior to challenge. Inhibition of rapid expulsion by irradiation 7 days prior to challenge was not reversed by immune serum and irradiation did not affect antibody titer in treated rats. It was suggested that irradiation 7 days before challenge compromised the intestinal, and not the immunological, component of rapid expulsion. Differences in sensitivity of “early” and “late” rapid expulsion to irradiation and cortisone therapy provide further evidence of functional differences between these rejection processes.

Regional lymph node metastasis in carcinoma of the hamster tongue

The incidence of regional lymph node metastasis in the hamster tongue carcinoma induced by DMBA was studied. Metastasis to the regional lymph node was confirmed by histologic examination in 25 (22.1%) of the 113 experimental animals. Of a total of 238 lymph nodes examined, metastatic deposits were found in 35 (14.6%) lymph nodes. Systemic administration of cortisone increased the rate of metastasis from 16.7% to 26.1%, but the difference was not statistically significant. The necessity of extending the tumor-bearing period and the addition of mechanical trauma to the primary carcinoma to increase the rate of metastasis are stressed.

Pathogenicity of Nocardia transvalensis for laboratory mice.

Nocardia transvalensis was found to be virulent for laboratory mice both by intraperitoneal and intravenous routes of inoculation, the latter route producing a more progressive and disseminating infection. Cortisone administration was found to enhance the susceptibility of mice, the LD50 for the cortisone treated mice being five times less than that for the untreated animals. In the tissues of cortisone treated mice, N. transvalensis grew as dispersed filaments with coccobacillary forms or sometimes their loose aggregates, whereas in normal animals granule formation was a conspicuous feature. The pathogenicity of N. transvalensis is compared with that of N. asteroides, N. brasiliensis and N. caviae from published reports.

Influence of glucocorticoids on calcium absorption in different segments of the rat intestine.

Glucocorticoids enhance the movement of fluid and sodium in the duodenum, thereby resulting in an increase in the passive transport of calcium. Since passive transport of calcium predominates in the distal intestinal segments, the influence of glucocorticoids on calcium and fluid transport in the duodenum, mid-jejunum, ileum, and colon of the rat was studied. Calcium transport and fluid absorption was determined by the in vivo ligated loop technique. One segment was ligated in each animal. Under either normal osmolarity or hypertonic conditions, administration of cortisone stimulated intestinal fluid absorption in each segment of the small intestine, but not in the colon. Since the final fluid sodium concentration was not altered, cortisone enhanced net sodium absorption in proportion to the increase in fluid transport. Glucocorticoids inhibited the active transport of calcium in the proximal regions of the small intestine by bidirectional changes in calcium flux. However, the inhibitory effect was not apparent under the conditions where passive transport predominates. The stimulation of passive transport in the mid-jejunum overcomes the inhibition of active transport. In the ileal region, glucocorticoids increased active transport of calcium by 165%, whereas the enhancement of calcium transport under conditions where passive transport predominated reached 217%. This result indicates that both active and passive transport of calcium were enhanced by glucocorticoid treatment. In the colon, glucocorticoids increased active transport by 170%. However, the magnitude of the increase in calcium transport was less under conditions where passive transport predominates (129%), indicating that glucocorticoids stimulate the active transport of calcium in the colon with no appreciable stimulation of passive transport.

Hamster cheek pouch carcinoma: effect of incision and cortisone on growth, invasion, and metastasis.

After cheek pouch carcinomas were induced in hamsters by the application of dimethylbenzanthracene (DMBA) to the right pouch for 13 weeks, the animals were divided into four groups and observed for seven more weeks. The control group received no further treatment, two experimental groups had incisional biopsies performed on tumors in their pouches, one of these also received injections of cortisone throughout the 20-week experimental period, and a fourth group received cortisone only. The wet weights of the cancerous cheek pouches were determined, and the submandibular and parotid salivary glands with associated cervical lymph nodes, the lungs, and the liver were examined with light microscopy. The cancerous pouches of the animals that received cortisone weighed significantly less than those of animals that received no cortisone but had incisional biopsies of the tumors. There was no significant difference in the degree of histodifferentiation of the tumors among the four groups. The animals in the two groups that received cortisone had significantly more tumors that were invasive than did the animals that did not receive cortisone. Cervical lymph node metastasis occurred in 21% to 38% of the animals but was not significantly different in the four groups. Distant metastases to the lungs or the liver were not found. Incisional biopsy of the tumors stimulated local growth of the cheek pouch tumors, and systemic cortisone administration produced more invasive cheek pouch tumors.

The effects of cortisone on immunity during chronic rodent malaria.

The temporal effects were studied of a single dose of hydrocortisone acetate on the development and expression of immune responses to Plasmodium berghei in mice with chronic infections. Cortisone administration prior to primary infection reduced malaria-specific secondary humoral and cellular responses, as well as the ability to survive parasite challenge. Once protective humoral immunity was established after chemotherapy of primary infection, cortisone treatment did not disrupt its expression. Administration of cortisone during subpatent chronic infection resulted in a transient recrudescence of parasitemia not apparent in untreated mice. Clearance of recrudescence or parasite challenge was associated with a rapid cortisone-resistant antibody response. During subpatent chronic infection, malaria-specific antibody levels were reduced, whereas delayed-type hypersensitivity (DTH) to malaria antigens and heterologous antigens was well developed. At least two systems of immunity to malaria appear to be present during chronic infection. Recrudescence of parasitemia may be prevented by antibody-independent, cortisone-sensitive cellular immunity. Once parasitemia becomes overt after cortisone treatment, or parasites are reintroduced with challenge, cortisone-resistant humoral immunity appears to mediate parasite clearance. Regulation of these systems may be a dose-dependent phenomenon which results in the persistence of parasites, albeit at subpatent levels.