Monocytes from patients with Primary Ciliary Dyskinesia show enhanced inflammatory properties and produce higher levels of pro-inflammatory cytokines.

Patients with Primary Ciliary Dyskinesia (PCD) suffer from recurrent upper and lower airway infections due to defects in the cilia present on the respiratory epithelium. Since chronic inflammatory conditions can cause changes in innate immune responses, we investigated whether monocytes isolated from the peripheral blood of pediatric PCD patients respond differently to inflammatory stimuli, compared to monocytes from healthy children and adults. The receptor for C5a (C5aR) was upregulated in PCD, whereas expression levels of the leukocyte chemoattractant receptors CCR1, CCR2, CCR5, BLT1 and FPR1 on PCD monocytes were similar to those on monocytes from healthy individuals. Also in vitro migration of PCD monocytes towards the ligands of those receptors (CCL2, fMLP, C5a and LTB4) was normal. Compared to healthy children, PCD patients had a higher percentage of the non-classic monocyte subset (CD14+CD16++) in circulation. Finally, PCD monocytes produced higher levels of pro-inflammatory cytokines (IL-1ß and TNF-α) and chemokines (CCL3, CCL5, CCL18 and CCL22) in response to LPS, peptidoglycan and/or dsRNA stimulation. These data suggest that monocytes might exacerbate inflammatory reactions in PCD patients and might maintain a positive feedback-loop feeding the inflammatory process.

11ß-hydroxysteroid dehydrogenase type 1 has no effect on survival during experimental malaria but affects parasitemia in a parasite strain-specific manner.

Malaria is a global disease associated with considerable mortality and morbidity. An appropriately balanced immune response is crucial in determining the outcome of malarial infection. The glucocorticoid (GC) metabolising enzyme, 11ß-hydroxysteroid dehydrogenase-1 (11ß-HSD1) converts intrinsically inert GCs into active GCs. 11ß-HSD1 shapes endogenous GC action and is immunomodulatory. We investigated the role of 11ß-HSD1 in two mouse models of malaria. 11ß-HSD1 deficiency did not affect survival after malaria infection, but it increased disease severity and parasitemia in mice infected with Plasmodium chabaudi AS. In contrast, 11ß-HSD1 deficiency rather decreased parasitemia in mice infected with the reticulocyte-restricted parasite Plasmodium berghei NK65 1556Cl1. Malaria-induced antibody production and pathology were unaltered by 11ß-HSD1 deficiency though plasma levels of IL-4, IL-6 and TNF-α were slightly affected by 11ß-HSD1 deficiency, dependent on the infecting parasite. These data suggest that 11ß-HSD1 is not crucial for survival of experimental malaria, but alters its progression in a parasite strain-specific manner.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases left ventricular function. An echocardiographic study in cancer patients.

To study the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the heart, echocardiographic assessments of left ventricular (LV) end-diastolic and end-systolic (ES) diameters (D), ejection fraction (EF) and cardiac output (CO) were done in six male patients (28-70 years of age) with advanced sarcoma (Group 1), prior to (day -1-0), during (day 7-9) and after (day 20-21) a first course of i.v. doxorubicin (day 0) without GM-CSF and a second course (3 weeks after the first one) with GM-CSF 250 microg/m(2)subcutaneously and daily from day 1-11. A similar study was done in ten female patients with advanced breast cancer (31-58 years of age, Group 2) for a first course of doxorubicin+cyclophosphamide with GM-CSF (same schedule as in Group 1). As compared to the mean of values prior to and after the course with GM-CSF in Group 1 and 2, the LVESD during GM-CSF administration transiently increased by median 6% (range -19 to 30%, P<0.05) vs -9% (-21 to 6%, not significant) in the first course without GM-CSF in Group 1 (P<0.05 between courses). The CO and EF tended to decrease during GM-CSF. GM-CSF thus causes a small and transient decrease of LV contractility.