DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical University of Gdańsk

Transcription

1 DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical University of Gdańsk Research group Head: Jolanta Myśliwska, MD, PhD Professor of immunology Joanna Więckiewicz, M. Sc. Dominik Rachoń, MD Łukasz Hak, M. Sc. Monika Mlotkowska, M.Sc. Katarzyna Zorena, PhD Hanna Suchanek, MD, PhD

2 RESEARCH PROBLEMS AGE-RELATED CHANGES OF IMMUNE RESPONSE HORMONAL MODULATION OF IMMUNE RESPONSE IMMUNOLOGICAL ASPECTS OF CARDIOVASCULAR DISEASE

3 PREVIOUS AND CURRENT

4 AGE-RELATED CHANGES OF IMMUNE RESPONSE ROLE OF NATURAL KILLER CELLS IN AGEING We found that successful healthy ageing is associated with a shift towards high cytotoxic activity of Natural Killer cells. The high values of NK-associated parameters may be preserved until very old age. Healthy elderly people have an increased number of the regulatory NK cells with intra-cellular IFN. This status correlates with anti-viral immune response in the elderly what we observed on the natural model of vaccination against influenza.

5 Myśliwska J, et al. (1997) Gerontology, 43, Myśliwska J, et al. (2000) Acta Biochem. Pol., 47, Kmieć Z, et al. (2001) Gerontology, 47, Brydak LB, et al. (2003) J. Clin. Immunol., 23: Myśliwska J, et al. (2003) Clin Exp. Immunol., accepted

6 PRO-INFLAMMATORY STATE IN THE ELDERLY We found that ageing process is accompanied by an enhanced expression of pro-inflammatory cytokines. Low immune response to vaccination in the elderly, who stayed apparently healthy, is associated with an increased expression of genes of such inflammatory cytokines as; Interleukin 1, TNF, Interleukin 6, Interleukin 12. Enhanced expression of pro-inflammatory cytokines was associated with carrier status of latent CMV infection in the elderly low responders to influenza vaccination. Myśliwska J, et al. (1999) Mech. Ageing Dev.,107: Myśliwska J, et al. (2000) Eur. Cytokine Net.,11: Trzonkowski P, et al. (2002) Mech. Ageing Dev.,123, Trzonkowski P, P et al. (2003) Vaccine, 21:

7 HORMONAL MODULATION OF IMMUNE RESPONSE ESTROGENS DOWN-REGULATE PRO-INFLAMMATORY AND UP- REGULATE ANTI-INFLAMMATORY CYTOKINES

8 Non-stimulated ex vivo monocytes of healthy postmenopausal women express the TNF gene 883bp 800bp 692bp -actin 501bp 420bp 404bp puc (-) (+) TNF This may be the effect of estrogen deprivation

9 Non-stimulated ex vivo monocytes of healthy postmenopausal women express the IL-6 gene 883bp 800bp 692bp 628bp 501bp (-) (+) -actin IL6 puc This may be the effect of an exaggerated TNF expression which in turn stimulates IL-6 gene expression Rachoń D, Myśliwska J, et al. (2002) J Endocrinol.,172,

10 Non-stimulated PBMC of postmenopausal women produce more bioactive TNF and IL-6 compared to young controls

11 In vitro effects of 17 -estradiol on the spontaneous TNF and IL-6 production by PBMC of postmenopausal women

12 In vivo effects of 17 -estradiol treatment on the spontaneous TNF and IL-6 production by PBMC of postmenopausal women

13 Non-stimulated PBMC of postmenopausal women produce less IL-10 compared to young controls

14 In vitro effects of 17 -estradiol on the IL-10 gene expression in the PBMC of postmenopausal women

15 CURRENT RESEARCH IMMUNOLOGICAL ASPECTS OF CARDIOVASCULAR DISEASE

16 Polymorphism of the human Interleukin 6 (IL6) gene at position 174G/C in coronary heart disease (CHD) patients years YEARS FROM ONSET OF THE DISEASE TILL AN OPERATION CC GG GC IL6 pg/ml 0 CONCENTRATION OF IL6 IN VITRO CULTURES CG and GG CC

17 Polymorphism of the human atrial natiuretic peptide (ANP) gene in coronary heart disease (CHD) patients Polymorphism is analysed in CHD patients with different cardiac arrhythmias occurring in (or without) association with cardiac surgery. The A2A2 allele combination carriers constitute 55% of the whole group of CHD patients and seem to be protective from atrial fibrillation.

18 21 bp 67 bp 111 bp 147 bp 190 bp 96 bp 117 bp 213 bp 242 bp 234 bp

19 INFECTIONS WITH CMV AND CHLAMYDIA PNEUMONIAE IN CHD PATIENS 185 bp positive control sample of mononuclear cells

20 ROLE OF CD14+CD16+ BLOOD MONOCYTES IN CORONARY HEART DISEASE Analysis of function of CD14+CD16+ monocytes detection of monocyte populations by cytophotometric technique tests revealing presence of intra-cytoplasmic cytokines in CD14+CD16+ monocytes in vitro cultures analysing an effect of Lovastatin on spontaneous and LPS-induced synthesis of intra-cytpolasmic IL6

21

22 CD14+CD16+ BLOOD monocytes in CORONARY C HEART DISEASE and controls % of CD14+CD16+ monocytes * patients controls Mediana 25%-75% Min.-Maks.

23 LPS-induced IL-6 production Spontaneous IL-6production * * Mediana Min.-Maks. CD14+ CD16+ * Control Lova LPS LPS + Lova 0 * CD14+ CD Mediana Min.-Maks. Mediana Min.-Maks Control Lova LPS LPS + Lova Mediana Min.-Maks.

24 Human cytokine array system expression profile of multiple cytokines positive control In serum of the patients with coronary heart disease, with CCS 3 and 4 grade of the angina pectoris, we found an expression of 18 new cytokines positive control