Titan zeichnet sich durch ein hervorragendes Korrosionsverhalten aus und hat dadurch
eine recht gute Verträglichkeit. Allerdings wissen sowohl Orthopäden als auch Zahnmediziner,
dass bei einigen Patienten die Implantate unerwünschte Entzündungserscheinungen induzieren,
die zur fehlenden knöchernen Integration führen können. Bis heute sind die verantwortlichen
Mechanismen der „Titan-Sensibilisierung“ nur teilweise bekannt. Echte Allergien auf
Titan stellen im Unterschied zu anderen Metallen eine Rarität dar. Titanionen bilden
durch ihre hohe Sauerstoffaffinität unmittelbar nach ihrer Freisetzung Oxide. Im Unterschied
zu freien Ionen können Oxide keine Proteinbindung eingehen, sind somit keine Haptene
und haben keine allergene Wirkung. Die häufigere Ursache der titaninduzierten Periimplantitis
ist die überschießende proentzündliche Reaktivität der Gewebemakrophagen nach Kontakt
mit Titan(oxid)partikeln, welche anhand der proentzündlichen Schlüsselzytokine Interleukin-1
und TNF-α sowohl in vivo (In-situ-Hybridisierung) als auch ex vivo (PBMC-Stimulationsüberstand)
messbar ist. Diese Zytokinantwort beruht nicht auf der Anwesenheit spezifischer Lymphozyten
(somit liegt definitionsgemäß keine Allergie vor), sondern auf einer erhöhten Entzündungsbereitschaft
unspezifischer Entzündungszellen (Gewebemakrophagen, Monozyten) nach Kontakt mit partikulärem
Titanabrieb (debris). Die Intensität, mit der die Gewebemakrophagen auf die Abrieb-Titanpartikel
mit einer Entzündung antworten, ist im Wesentlichen genetisch geprägt. Die vorliegende
Arbeit gibt den aktuellen Stand der wissenschaftlichen Literatur zum Thema „Immunologie
des Titans“ wieder.
One of the main reasons for the high immunological tolerance of Titan in comparence
to other metals is its excellent corrosive behaviour. On the other side it is well
known by orthopedists and dentists that in some patients titanium implants induce
inflammatory reactions that not seldom cause the integration of the implant to fail.
Until today the responsible mechanisms of this „titanium sensibilisation“ are only
partially known. Contrary to allergies towards other metals, real cellular induced
allergies for titan are very seldom. Due to their high affinity to oxygen, titan-ions
directly after their release form oxides. Other than free ions, oxides can not bind
to proteins en therefore can not act as a hapten.
A common cause of this „titanium sensibilisation“ is the exaggerated pro-inflammatory
reactivity of tissue-macrophages after contact with titan(oxid)particles. This reaction
is as well in vivo as in vitro measurable by the pro-inflammatory key-cytokines interleucine-1
and TNF-α. The cytokine response is not caused by the presence of specific lymphocytes
but is based upon an enhanced inflammatory readiness of unspecific inflammatory cells
after contact with debris (titan-particle-abrasion). The intensity of the inflammatory
reaction of tissue-macrophages towards titan-particle-abrasion is mainly dependant
upon genetical factors.
Schlüsselwörter
Titan - Entzündung - Makrophagen - Genpolymorphismus - Periimplantitis - Abrieb -
Allergie
Key words
Titanium - Inflammation - Macrophages - Gene Polymorphism - Peri-implantitis - Debris
- Allergy
Literatur
1
Agrup G..
Sensitization induced by patch testing.
Br J Dermatol.
1968;
80
631-634
2
Basketter DA, Whittle E, Monk B..
Possible allergy to complex titanium salt.
Contact Dermatitis.
2000;
42
310-311
3
Brune D..
Metal release from dental biomaterials.
Biomaterials.
1986;
7
163-175
4
Carlsson AS, Magnusson B, Möller H..
Metal sensitivity in patients with metal-to-plastic total hip arthroplasties.
Acta Orthop Scand.
1980;
51
57-62
5
Catelas L..
In vitro induction of macrophage cytokine release by ceramic and polyethylene particles.
44th Annual meeting, Orthopaedic Research Society, New Orleans, Lousiana.
1998;
6
Dörner T, von Baehr V et al..
Implant-related inflammatory arthritis.
Nature Clin Pract Rheumatol.
2006;
2
53
7
Eis D. et al..
Qualitätssicherung beim Lymphozytentransformationstest – Bundegesundheitsblatt.
2008;
51
1070-1076
8
Feloutzis A, Lang NP, Tonetti MS et al..
IL-1 gene polymorphism and smoking as risk factors for peri-implant bone loss in a
well-maintained population.
Clin Oral Implants Res.
2003;
14
10-17
9
Frisken KW, Dandie GW, Lugowski S et al..
A study of titanium release into body organs following the insertion of single threaded
screw implants into the mandibles of sheep.
Aust Dent J.
2002;
47
214-217
10
Hallab N..
Metal sensitivity in patients with orthopedic implants.
J Clin Rheumatol.
2001;
7
215-218
11
Huang HH, Chiu YH, Lee TH et al..
Ion release from NiTi orthodontic wires in artificial saliva with various acidities
Biomaterials.
2003;
24
3585-3592
12
Ingham E, Fisher J..
The role of macrophages in osteolysis of total joint replacement.
Biomaterials.
2005;
26
1271-1286
13
Lindemann M, Rietschel F, Zabel M et al..
Detection of chromium allergy by cellular in vitro methods.
Clin Exp Allergy.
2008;
38
1468-1475
14
Matthew IR, Frame JW, Browne RM et al..
In vivo surface analysis of titanium and stainless steel miniplates and screws.
Int J Oral Maxillofac Surg.
1996;
25
463-468
15
Merkel KD, Erdmann JM, McHugh KP et al..
Tumor necrosis factor-alpha mediates orthopedic implant osteolysis.
Am J Pathol.
1999;
154
203-210
16
Nakashima Y, Sun DH, Trindade MC et al..
Signaling pathways for tumor necrosis factor-alpha and interleukin-6 expression in
human macrophages exposed to titanium-alloy particulate debris in vitro.
J Bone Joint Surg Am.
1999;
81
603-315
17
Perala DG, Chapman RJ, Gelfand JA et al..
Relative production of IL-1 beta and TNF alpha by mononuclear cells after exposure
to dental implants.
J Periodontol.
1992;
63
426-430
18
Rader CP, Sterner T, Jakob F et al..
Cytokine response of human macrophage-like cells after contact with polyethylene and
pure titanium particles.
J Arthroplasty.
1999;
14
840-848
19
Rakshit DS, Lim JT, Ly K et al..
Involvement of complement receptor 3 (CR3) and scavenger receptor in macrophage responses
to wear debris.
J Orthop Res.
2006;
24
2036-2044
20
Schuh A, Thomas P, Kachler W et al..
Allergic potential of titanium implants.
Orthopade.
2005;
34
327-328
21
Solar RJ, Pollack SR, Korostoff E..
In vitro corrosion testing of titanium surgical implant alloys: an approach to understanding
titanium release from implants.
J Biomed Mater Res.
1979;
13
217-250
22
Soysa NS, Alles N..
NF-kappaB functions in osteoclasts.
Biochem Biophys Res Commun.
2009;
378
1-5
23
Swiontkowski MF, Agel J, Schwappach J et al..
Cutaneous metal sensitivity in patients with orthopaedic injuries.
Orthop Trauma.
2001;
15
86-89
24
Thomas P, Bandl WD, Maier S et al..
Hypersensitivity to titanium osteosynthesis with impaired fracture healing, eczema,
and T-cell hyperresponsiveness in vitro: case report and review of the literature.
Contact Dermatitis.
2006;
55
199-202
25
Torgersen S, Gjerdet NR, Erichsen ES et al..
Metal particles and tissue changes adjacent to miniplates. A retrieval study.
Acta Odontol Scand.
1995;
53
65-71
26
Tuan RS, Lee FY, T Y Konttinen et al..
What are the local and systemic biologic reactions and mediators to wear debris, and
what host factors determine or modulate the biologic response to wear particles? Implant
Wear Symposium 2007 Biologic Work Group.
J Am Acad Orthop Surg.
2008;
16
(S 01)
42-48
27
Wataha J..
Materials for endosseous dental implants.
J Oral Rehabil.
1996;
23
79-90
28
Wei X, Zhang X, Zuscik MJ et al..
Fibroblasts express RANKL and support osteoclastogenesis in a COX-2-dependent manner
after stimulation with titanium particles.
J Bone Miner Res.
2005;
20
1136-1148
29
Weingart D, Steinemann S, Schilli W et al..
Titanium deposition in regional lymph nodes after insertion of titanium screw implants
in maxillofacial region.
Int J Oral Maxillofac Surg.
1994;
23
450-452
30
Wennerberg A, Ide-Ektessabi A, Hatkamata S et al..
Titanium release from implants prepared with different surface roughness.
Clin Oral Implants Res.
2004;
15
505-512
31
Willert HG, Buchhorn GH, Hess T..
The significance of wear and material fatigue in loosening of hip prostheses.
Orthopäde.
1989;
18
350-369
32
Xing Z, Schwab LP, Alley CF et al..
Titanium particles that have undergone phagocytosis by macrophages lose the ability
to activate other macrophages.
J Biomed Mater Res B Appl Biomater.
2008;
85
37-41
Korrespondenzadresse
Dr. Volker von Baehr
Immunologie und Allergologie am Institut für Medizinische Diagnostik Berlin
Nicolaistraße 22
12247 Berlin
Email: v.baehr@imd-berlin.de