Biomedical subjects

Johan Garssen

Publications and source records attributed to Johan Garssen.

24 records · Page 2Linked to original sources

PubMed2002

Ultraviolet radiation, resistance to infectious diseases, and vaccination responses.

Exposure to ultraviolet (UV) radiation, as in sunlight, can modulate immune responses in animals and humans. This immunomodulation can lead to positive health effects especially with respect to certain autoimmune diseases and allergies. However, UV-induced immunomodulation has also been shown to be deleterious. Experimental animal studies have revealed that UV exposure can impair resistance to many infectious agents, such as bacteria, parasites, viruses, and fungi. Importantly, these effects are not restricted to skin-associated infections, but also concern systemic infections. The real consequences of UV-induced immunomodulation on resistance to infectious diseases are not known for humans. Risk estimations have been performed through extrapolation of animal data, obtained from infection models, to the human situation. This estimation indicated that UV doses relevant to outdoor exposure can impair the human immune system sufficiently to have effects on resistance to infections. To further quantify and validate this risk estimation, data, e.g., from human volunteer studies, are necessary. Infection models in humans are not allowed for ethical reasons. However, vaccination against an infectious disease evokes a similar immune response as the pathogen and thereby provides an opportunity to measure the effect of UV radiation on the immune system and an estimate of the possible consequences of altered resistance to infectious agents. Effects of controlled UVB exposure on immune responses after hepatitis B vaccination have been established in mice and human volunteers. In mice, cellular and Th1-associated humoral immune responses to hepatitis B were significantly impaired, whereas in human volunteers no significant effect of UVB on these responses could be found. Preliminary data indicate that cytokine polymorphisms might be, at least in part, responsible for interindividual differences in immune responses and in susceptibility to UVB-induced immunomodulation. In addition, adaptation to UV exposure needs to be considered as a possible explanation for the difference between mice and humans that was observed in the hepatitis B vaccination model.

Adaptation, Physiological↗

PubMed2002

Exposure to solar ultraviolet radiation in young Dutch children: assessment by means of a 6-week retrospective questionnaire.

We designed a 6-week retrospective questionnaire on sunlight exposure. Estimation of the short-term exposure to sunlight is important for observational human studies concerning the effects of ultraviolet radiation (UVR) on the human immune system and related resistance to infections. This questionnaire was given to the parents of 1672 1-year-old children in the Netherlands who participated in a birth cohort study. We evaluated the questionnaire and estimated the personal 6-week cumulative exposure to solar UVR. Only 910 questionnaires (54.4%) were filled out completely and consistently. This suggests that reporting data on children's outdoor exposure, even for the recent past, is often difficult. The data from these questionnaires indicated that the crude number of reported outdoor hours was enough to obtain a relative estimate of the individual exposure to ambient UVR, but that weighting for the effect of clothing was essential for the classification of the systemic UVR dosage received. Sunny weeks in the Netherlands in 1998, as were established by independent measurements of the levels of ambient UVR, vacations abroad, and sunburn, were associated with a comparatively high mean estimated exposure. These results support the suitability of the questionnaire for classifying the participants with respect to their short-term exposure to solar UVR.

Cohort Studies↗

PubMed2002

Application of a systemic herpes simplex virus type 1 infection in the rat as a tool for sunscreen photoimmunoprotection studies.

The application of a novel model for sunscreen photoimmunoprotection studies was assessed using a systemic infection of rats with herpes simplex virus type 1 (HSV-1). Rats were irradiated daily with 1 minimal erythemal/oedematous dose of UVB for 7 consecutive days on their shaved backs with or without application of a broad-spectrum sunscreen (containing TiO2) with a sun protection factor of 10. Subsequently, rats were infected intranasally with HSV. UV exposure prior to HSV infection induced increased severity and incidence of clinical signs of disease, suppression of cellular immune responses as assessed by delayed type hypersensitivity and increased viral load in the brain. The sunscreen provided protection against all these UV-induced effects. We conclude that this novel model is a promising way of testing the immunoprotective qualities of sunscreens, based on the response to a common infectious agent of human subjects.

Animals↗

PubMed2002

A quantitative model for neutrophil response and delayed-type hypersensitivity reaction in rats orally inoculated with various doses of Salmonella Enteritidis.

Our aim was to investigate the quantitative relationship between inoculation doses and physiological responses to infection by Salmonella enterica serovar Enteritidis. Rats were orally inoculated with 10-10(9) c.f.u. of S. Enteritidis and monitored for 6 days. Neutrophil and delayed-type hypersensitivity (DTH) responses were assessed, and the spleens were analyzed for the pathogen. The experimental data were analyzed by a mathematical model for the host response to salmonella infection, which is based on the assumptions that: (i) the number of pathogens in the inoculum is Poisson distributed, (ii) any cell that is inoculated can multiply and form a clone to infect the animal, (iii) the probability of infection by any cell of the pathogen is independent of the number of cells ingested, and (iv) the magnitude of the immune response increases with dose, but eventually saturates to a maximum level. The probability of infection assessed by the DTH response is 7.5 x 10(-3)/c.f.u. of the inoculum (confidence interval 5.1 x 10(-5), 1.2 x 10(-2)). When five S. Enteritidis independently initiated the infection, the DTH response to the resulting clones of the salmonellae saturated to the maximum level. The probability of infection assessed by the neutrophil response is 3.4 x 10(-4)/c.f.u. (1.0 x 10(-4), 6.8 x 10(-4)). The response saturated when six S. Enteritidis independently initiated the infection. The probability of infection assessed by the analysis of spleens is 1.2 x 10(-3)/c.f.u. (4.1 x 10(-4), 2.6 x 10(-3)). We conclude that at low inocula, infections are initiated by very small numbers of bacteria. The magnitude of the immune responses is similar whether only a few or a larger number of bacteria initiated the infection.

Animals↗

PubMed2002

UVB exposure impairs immune responses after hepatitis B vaccination in two different mouse strains.

Ultraviolet light exposure can impair immune responses that are not restricted to the exposed skin but is also found at other sites, i.e. systemic immunosuppression. Therefore, we investigated the UV-induced modulating effects on vaccination against hepatitis B in a mouse model. Two different mouse strains, BALB/c and C57B1/ 6, were vaccinated intramuscularly against hepatitis B. Mice were exposed to different doses of ultraviolet B (UVB) for five consecutive days on shaved back skin before the vaccination. Vaccination against hepatitis B induced cellular (delayed-type hypersensitivity [DTH] and lymphocyte stimulation test) as well as humoral immune responses in both mouse strains. The DTH responses in C57BB1/6 mice were statistically significantly higher compared with BALB/c mice. UVB exposure induced a dose-dependent suppression of cellular immunity in both strains of mice. C57B1/6 mice seemed to be more susceptible to this suppression. Anti-hepatitis B surface antibodies (total-Ig) were only marginally suppressed after UVB exposure. IgG2a and interferon-gamma levels, both indicators for Th1 immune response, were suppressed in both mouse strains after UVB exposure. In summary, UVB exposure induced a dose-dependent suppression of both cellular and humoral immune responses after hepatitis B vaccination, although the suppressive effects on humoral immunity were limited to IgG2a production. Susceptibility to UVB-induced immunomodulation depended on the strain of mice and their predilection for developing different T cell responses.

Animals↗

PubMedDate not supplied

Suppression of different phases of systemic contact hypersensitivity by urocanic acid oxidation products.

On exposure to UV-B, the epidermal component trans-urocanic acid (UCA) is not only photoisomerized into cis-UCA but will also, at least in part, be photooxidized into UCA oxidation products (UOPs). We hypothesized that UOPs can mimic UV-induced systemic immunosuppression comparable to the suppressive properties already established for cis-UCA. A crude mixture of UOPs showed a significant suppression of the sensitization phase of the systemic contact hypersensitivity (CHS) response to picryl chloride (PCl). Three of the UOPs were selected for this study: imidazole-4-carboxylic acid (ImCOOH), imidazole-4-carboxaldehyde (ImCHO) and imidazole-4-acetic acid (ImAc). Effects on the sensitization, elicitation and postelicitation phases of CHS to PCl in BALB/c mice were studied and compared with the effects of cis-UCA. ImCHO was equally effective at suppressing the sensitization phase as cis-UCA. The triplet combination of the imidazoles (1:1:1) showed more pronounced suppression than that induced by cis-UCA. The most effective compounds for the suppression of the elicitation phase appeared to be ImAc and cis-UCA. Significant suppression of the postelicitation phase was only obtained with the triplet combination of ImCHO, ImCOOH and ImAc, the combination that appeared to be effective at all three tested phases. Because these three UOPs are present in UV-B-exposed human stratum corneum, these compounds may play a role in UV-B-induced immunosuppression.

Animals↗