Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia.

Pathogenesis of invasive candidiasis may involve regulatory activities of Th2 immunity on phagocytic host defenses. The effects of interleukin (IL)-4 on antifungal capacity of human mononuclear phagocytes against Candida albicans were studied. Incubation of adherent mononuclear leukocytes from healthy donors with IL-4 (1-5 ng ml(-1)) at 37 degrees C for 2-4 days suppressed uptake of C. albicans blastoconidia in the presence of human serum (P < or = 0.01), and anti-IL-4 inhibited its suppressive effect. The effect of IL-4 was protein synthesis-dependent. Interferon-gamma (0.25-25 ng ml(-1)), granulocyte-macrophage colony-stimulating factor (CSF, 20 ng ml(-1)), macrophage-CSF (15 ng ml(-1)) but not IL-10 (100 ng ml(-1)) somewhat counteracted the suppressive effect of IL-4. In contrast, mannose receptor-mediated uptake of blastoconidia in the absence of serum was increased by IL-4. Killing of conidia was decreased after incubation of morphonuclear leukocytes with IL-4 for 2 days (P < 0.05). While superoxide anion production in response to phorbol myristate acetate was decreased by IL-4 (P < 0.05), it was not altered in response to blastoconidia and pseudohyphae. Morphonuclear leukocyte-induced pseudohyphal damage also remained unaltered. These findings suggest that IL-4 plays its detrimental role in invasive candidiasis by predominantly suppressing uptake and killing of blastoconidia by morphonuclear leukocytes. Anti-IL-4, IFN-gamma, GM-CSF and M-CSF appear to counteract suppression of morphonuclear leukocyte phagocytic activity suggesting new approaches to the management of disseminated candidiasis.

IL-10 exerts suppressive and enhancing effects on antifungal activity of mononuclear phagocytes against Aspergillus fumigatus.

Invasive aspergillosis has emerged as a frequent and serious infection in immunocompromised patients. We studied the effects of human IL-10 on antifungal activity of monocytes (MNCs) from healthy adults against Aspergillus fumigatus after incubation with IL-10 at 37 degrees C for 2 to 4 days. IL-10 (2-20 ng/ml)-pretreated MNCs exhibited approximately 40% suppression of superoxide anion (02-) production in response to PMA and FMLP (p < or = 0.003), and anti-IL-10 containing supernatant neutralized the IL-10 effect. IL-10 (20 ng/ml)-pretreated MNCs exhibited decreased damage of Aspergillus hyphae after 2 to 4 days (55-98% decrease, p < or = 0.04). The MNC phagocytic activity against conidia, as assessed by microscopy (percentage of phagocytosing MNCs and number of intracellular conidia per MNC) as well as by colony counting (colonies grown from intracellular conidia), was enhanced by 127% (p = 0.006), 14% (p = 0.03), and 23% (p = 0.009), respectively. MNC capacity to inhibit intracellular germination was marginally enhanced (p = 0.04) and intracellular conidiocidal activity was unaffected by IL-10. IL-4 (5 ng/ml) did not change the up-regulatory IL-10 effect on phagocytosis. IFN-gamma (25 ng/ml) and granulocyte-macrophage CSF (20 ng/ml), but not macrophage CSF (15 ng/ml), appeared to counteract suppressive IL-10 effects. Thus, IL-10 suppresses oxidative burst and antifungal activity of MNCs against Aspergillus hyphae, while increasing their phagocytic activity. These findings further elucidate a potential role of IL-10 in the pathogenesis of invasive aspergillosis, which may lead to new treatment strategies.

Plasma exchange (PE) treatment in drug-induced toxic epidermal necrolysis (TEN).

Toxic epidermal necrolysis (TEN) or Lyell's syndrome is a rare fulminating skin disease notorious for its rapidly progressive course and high mortality rate. TEN is characterized by the sudden onset of epithelial necrosis of skin with frequently associated involvement of the gastrointestinal, genitourinary tract and bronchopulmonary linings. We describe the clinical course of five patients with severe drug-induced TEN, treated with PE. The suspected drugs were carbamazepine in one patient, paracetamol in one, a combination of paracetamol and mefenamic acid in one, allopurinol in one and ciprofloxacin in one. Three had a skin involvement affecting almost the entire surface of the body. In addition to the skin lesions, mouth, esophagus and lungs were also involved. Steroids proved ineffective. PE was carried out because of the rapid deterioration of the clinical picture. The mean number of PE sessions was 3.22 (range 1-5). Complete remission of the syndrome was achieved in four patients. One patient died due to septic shock. As so far there is no treatment of proven value for this condition, controlled trials should be set up in order to assess the value of PE in TEN.

Familial hypobetalipoproteinaemia.

Familial hypobetalipoproteinaemia is a rare condition and is usually asymptomatic in heterozygotes. We report a case of hypobetalipoproteinaemia in an 8-month-old boy presenting with diarrhoea and failure to thrive since birth, who has been successfully treated with dietary restriction and large oral doses of vitamin E. This disease is one of the causes of chronic diarrhoea in childhood and its early treatment probably prevents irreversible retinal and nervous system lesions in later life.

Factors affecting the peak expiratory flow rate in children.

Standing height and peak expiratory flow rate (PEFR) were measured in 339 British schoolchildren aged 7-16 years. Enquiry was made into a past history of wheeze or atopy, a family history of asthma or atopy, or a cold within the preceding 2 weeks. A strong correlation was found between PEFR and height, expressed by the equation PEFR = 5.640 Ht - 472.5 (r = 0.89). Neither a recent cold nor a positive personal or family history of wheeze or atopy had any significant effect on the regression equation. Sex was also unimportant. Further examination of the data revealed that age had an effect on peak expiratory flow rate independent of height. The effect of age was linear in girls and curvilinear in boys. Five hundred and sixty-nine Greek schoolchildren were also studied and similar age effects were found on the regression of peak expiratory flow rate on height. The implication of these findings is that any population study of peak expiratory flow rates in children should ensure a normal age distribution at each height interval. Significant error in the prediction of the PEFR will result if the effect of age is ignored, particularly in pubertal boys.

Unexpectedly high peak expiratory flow rates in normal Greek children.

Peak expiratory flow rate (PEFR) and standing height (Ht) were measured in 522 healthy Greek children aged 7-16 years. The regression equation of PEFR on height in centimetres was PEFR = 5.34 Ht--380.8. This demonstrated markedly higher values for PEFR in Greek children compared to previously published data from other countries. A sample of 339 British children was examined similarly. The regression equation of PEFR on height in centimetres was PEFR = 5.64 Ht--472.5. This was similar to previously published data. No cause for this discrepancy was found after close examination of population sampling, measurement error or calibration error in the Greek study. It is therefore concluded that Greek children appear to have an unexpectedly high PEFR for height.

Granulosa-theca-cell tumour in a 17-month-old girl.

A granulosa-theca-cell tumour in a 17-month-old girl with isosexual precocity and hirsutism is described. Following removal of the tumour, pubertal signs and hirsutism gradually subsided. Serum alpha-fetoprotein was very high (1800 ng/ml) before, but not any longer detectable after the removal of the tumour and on repeated measurements for the subsequent 34 months, at which time the clinical condition of the child has been very good.

Pseudo-vitamin D deficiency rickets: report of a case.

A 19-month-old boy with repeated convulsions from the age of 7 months was found to have pseudo-vitamin D deficiency rickets. The convulsions were attributed to hypocalcaemia which is one of the main features of this type of rickets. High doses of vitamin D produced clinical, biochemical and radiographic cure.

Defective neutrophil chemotaxis and hyperimmunoglobulinemia E in a child with recurrent infections.

The clinical and immunologic features of an adolescent boy with recurrent pyogenic infections are presented. A cellular defect in neutrophil chemotaxis, hyperimmunoglobulinemia E, and a negative delayed cutaneous reaction to antigen from Candida albicans were found.

Raised IgA in idiopathic pulmonary haemosiderosis.

Levels of immunoglobulin G, A, and M were studied in 31 children with idiopathic pulmonary haemosiderosis and in 35 relatives. A selective increase in serum IgA was observed in the patients. IgA levels in saliva did not show any difference compared with those of normal children.