Biomedical subjects

N E Denecker

Publications and source records attributed to N E Denecker.

3 recordsLinked to original sources

PubMed1998

Modulation of the pro- and anti-inflammatory cytokine balance by amphotericin B.

Amphotericin B is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha). We assessed the capacity of amphotericin B to modulate production of these pro-inflammatory cytokines as well as the anti-inflammatory IL-1 receptor antagonist (IL-1ra), induced by LPS, heat-killed Candida albicans or Staphylococcus aureus. The results of the present study show that amphotericin B slightly increased the production of pro-inflammatory cytokines by human mononuclear cells (PBMC), whereas the production of the anti-inflammatory cytokine IL-1ra was significantly inhibited. This results in a shift towards pro-inflammatory cytokine production, as indicated by a decreased IL-1ra/IL-1beta ratio. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) indicated that levels of IL-1beta and TNFalpha mRNA were increased. In conclusion, amphotericin B is able to cause a shift towards pro-inflammatory cytokine production by human PBMC. This may explain the side effects, such as fever and chills, observed after treatment of patients with amphotericin B.

Amphotericin B↗

PubMed1997

Regulation of the production of pro-inflammatory cytokines and antagonists during chemotherapy-induced neutropenia in patients with haematological malignancies.

Cytokine profiles were studied during 19 episodes of chemotherapy-induced neutropenia in 17 patients with haematological malignancies. Circulating concentrations of interleukin 1 alpha (IL-1 alpha), tumour necrosis factor alpha (TNF-alpha) and IL-1 receptor antagonist (IL-1ra) were measured before chemotherapy and thereafter three times weekly. During and after chemotherapy no significant changes were found in circulating cytokines. After start of chemotherapy, the ex-vivo LPS-stimulated production of cytokines in whole blood decreased and subsequently disappeared completely in all patients, and recovered after the end of treatment. The decrease of cytokine production could not be attributed to the decreased number of cells only, as the net production per circulating neutrophil or monocyte also decreased significantly, and was restored after completion of chemotherapy. These results show that the production of IL-1 beta, TNF-alpha and IL-1ra in blood disappears during chemotherapy-induced neutropenia, not only due to the decreased number of producing cells, but also as a result of a decreased production per cell, suggesting a mechanism of downregulation.

Adrenal Cortex Hormones↗

PubMed1995

[Hyperimmunoglobulin D syndrome].

The hyper-IgD syndrome is a rare entity characterized by early onset of attacks of periodic fever. All patients have an elevated serum IgD (> 100 U/ml). Symptoms during attacks include joint involvements (arthralgias/arthritis), abdominal complaints (vomiting, pain, diarrhoea), skin lesions, swollen lymph nodes, and headache. In 1992 an International hyper-IgD study group was established, and to date the diagnosis has been made in 60, mainly European patients; 14 come from France. The disorder occurs in families and is transmitted by autosomal recessive inheritance. Linkage studies indicate that the gene encoding for familial Mediterranean fever is different from the gene for the hyper-IgD syndrome. In children the hyper-IgD syndrome should be distinguished from two other periodic febrile disorders. CINCA (chronic inflammatory, neurological, cutaneous and articular syndrome) and FAPA (periodic fever, adenopathies, pharyngitis, and aphtous stomatitis) share some symptoms with the hyper-IgD syndrome but in these syndromes serum IgD is normal. The pathogenesis remains to be elucidated but during attacks all patients have an acute-phase response with elevated C-reactive protein concentrations. During the febrile episodes, the inflammatory cytokines such as IL-6 TNF alpha, IFN gamma are increased together with natural occurring inhibitors such as IL-1ra and sTNFr. There is no therapy for the syndrome and patients will experience attacks during their entire life although frequency and severity tend to diminish with age.

Female↗